Science.gov

Sample records for vacuum freeze drying

  1. Comparison of drying characteristic and uniformity of banana cubes dried by pulse-spouted microwave vacuum drying, freeze drying and microwave freeze drying.

    PubMed

    Jiang, Hao; Zhang, Min; Mujumdar, Arun S; Lim, Rui-Xin

    2014-07-01

    To overcome the flaws of high energy consumption of freeze drying (FD) and the non-uniform drying of microwave freeze drying (MFD), pulse-spouted microwave vacuum drying (PSMVD) was developed. The results showed that the drying time can be dramatically shortened if microwave was used as the heating source. In this experiment, both MFD and PSMVD could shorten drying time by 50% as compared to the FD process. Depending on the heating method, MFD and PSMVD dried banana cubes showed trends of expansion while FD dried samples demonstrated trends of shrinkage. Shrinkage also brought intensive structure and highest fracturability of all three samples dried by different methods. The residual ascorbic acid content of PSMVD dried samples can be as high as in FD dried samples, which were superior to MFD dried samples. The tests confirmed that PSMVD could bring about better drying uniformity than MFD. Besides, compared with traditional MFD, PSMVD can provide better extrinsic feature, and can bring about improved nutritional features because of the higher residual ascorbic acid content. © 2013 Society of Chemical Industry.

  2. Development of a compact freeze vacuum drying for jelly fish (Schypomedusae)

    NASA Astrophysics Data System (ADS)

    Alhamid, M. Idrus; Yulianto, M.; Nasruddin

    2012-06-01

    A new design of a freeze vacuum drying with internal cooling and heater from condenser's heat loss was built and tested. The dryer was used to dry jelly fish (schypomedusae), to study the effect of drying parameters such as the temperature within the drying chamber on mass losses (evaporation) during the freezing stage and the moisture ratio at the end of the drying process. The midili thin layer mathematical drying model was used to estimate and predict the moisture ratio curve based on different drying chamber temperatures. This experiment shows that decreasing the drying chamber temperature with constant pressure results in less mass loss during the freezing stage Drying time was reduced with an increase in drying temperature. Decreasing the drying chamber temperature results in lower pressure saturation of the material has no effect of drying chamber pressure on mass transfer.

  3. Key composition optimization of meat processed protein source by vacuum freeze-drying technology.

    PubMed

    Ma, Yan; Wu, Xingzhuang; Zhang, Qi; Giovanni, Vigna; Meng, Xianjun

    2018-05-01

    Vacuum freeze-drying technology is a high technology content, a wide range of knowledge of technology in the field of drying technology is involved, it is also a method of the most complex drying equipment, the largest energy consumption, the highest cost of drying method, but due to the particularity of its dry goods: the freeze-drying food has the advantages of complex water performance is good, cooler and luster of freezing and drying food to maintain good products, less nutrient loss, light weight, easy to carry transportation, easy to long-term preservation, and on the quality is far superior to the obvious advantages of other dried food, making it become the forefront of drying technology research and development. The freeze-drying process of Chinese style ham and western Germany fruit tree tenderloin is studied in this paper, their eutectic point, melting point and collapse temperature, freeze-drying curve and its heat and mass transfer characteristics are got, then the precool temperature and the highest limiting temperature of sublimation interface are determined. The effect of system pressure on freeze-dried rate in freeze-drying process is discussed, and the method of regulating pressure circularly is determined.

  4. A New Freezing Method Using Pre-Dehydration by Microwave-Vacuum Drying

    NASA Astrophysics Data System (ADS)

    Tsuruta, Takaharu; Hamidi, Nurkholis

    Partial dehydration by microwave-vacuum drying has been applied to tuna and strawberry in order to reduce cell-damages caused by the formation of large ice-crystals during freezing. The samples were subjected to microwave vacuum drying at pressure of 5 kPa and temperature less than 27°C to remove small amount of water prior to freezing. The tuna were cooled by using the freezing chamber at temperature -50°C or -150°C, while the strawberries were frozen at temperature -30°C or -80°C, respectively. The temperature transients in tuna showed that removing some water before freezing made the freezing time shorter. The observations of ice crystal clearly indicated that rapid cooling and pre-dehydration prior to freezing were effective in minimizing the size of ice crystal. It is also understood that the formation of large ice crystals has a close relation to the cell damages. After thawing, the observation of microstructure was done on the tuna and strawberry halves. The pre-dehydrated samples showed a better structure than the un-dehydrated one. It is concluded that the pre-dehydration by microwave-vacuum drying is one promising method for the cryo-preservation of foods.

  5. Comparison of three-dimensional printing and vacuum freeze-dried techniques for fabricating composite scaffolds

    SciT

    Sun, Kai; Li, Ruixin; Jiang, Wenxue, E-mail: jiangortholivea@sina.cn

    In this study, the performances of different preparation methods of the scaffolds were analyzed for chondrocyte tissue engineering. Silk fibroin/collagen (SF/C) was fabricated using a vacuum freeze-dried technique and by 3D printing. The porosity, water absorption expansion rates, mechanical properties, and pore sizes of the resulting materials were evaluated. The proliferation and metabolism of the cells was detected at different time points using an MTT assay. Cell morphologies and distributions were observed by histological analysis and scanning electron microscopy (SEM). The porosity, water absorption expansion rate, and Young’s modulus of the material obtained via 3D printing were significantly higher thanmore » those obtained by the freeze-dried method, while the pore size did not differ significantly between the two methods. MTT assay results showed that the metabolism of cells seeded on the 3D printed scaffolds was more viable than the metabolism on the freeze-dried material. H&E staining of the scaffolds revealed that the number of cells in the 3D printed scaffold was higher in comparison to a similar measurement on the freeze-dried material. Consequently, stem cells grew well inside the 3D printed scaffolds, as measured by SEM, while the internal structure of the freeze-dried scaffold was disordered. Compared with the freeze-dried technique, the 3D printed scaffold exhibited better overall performance and was more suitable for cartilage tissue engineering. - Highlights: • Silk fibroin/collagen was fabricated using 3D printing. • Physical characterization and Cell compatibility were compared. • 3D printed scaffold exhibited better overall performance.« less

  6. Analysis of the moisture evaporation process during vacuum freeze-drying of koumiss and shubat

    NASA Astrophysics Data System (ADS)

    Shingisov, Azret Utebaevich; Alibekov, Ravshanbek Sultanbekovich

    2017-05-01

    The equation for the calculating of a moisture evaporation rate in the vacuum freeze-drying, wherein as a driving force instead of the generally accepted in the drying theory of Δt temperature difference, Δp pressure difference, Δc concentration difference, a difference of water activity in the product and the relative air humidity (a_{{w}} - \\varphi) is suggested. By using the proposed equation, the processes of vacuum freeze-drying of koumiss and shubat were analyzed, and it was found two drying periods: constant and falling. On the first drying period, a moisture evaporation rate of koumiss is j = 2.75 × 10-3 kg/(m2 h) and of shubat is j = 2.37 × 10-3 kg/(m2 h). On the second period, values decrease for koumiss from j = 2.65 × 10-3 kg/(m2 h) to j = 1.60 × 10-3 kg/(m2 h), and for shubat from j = 2.25 × 10-3 kg/(m2 h) to j = 1.62 × 10-3 kg/(m2 h). Specific humidity for koumiss is ueq = 0.61 kg/kg and for shubat is ueq = 0.58 kg/kg. The comparative analyze of the experimental data of the moisture evaporation rate versus the theoretical calculation shows that the approximation reliability is R2 = 0.99. Consequently, the proposed equation is useful for the analyzing a moisture evaporation rate during a vacuum freeze-drying of dairy products, including cultured milk foods.

  7. Changes in non-volatile taste components of button mushroom (Agaricus bisporus) during different stages of freeze drying and freeze drying combined with microwave vacuum drying.

    PubMed

    Pei, Fei; Shi, Ying; Gao, Xingyang; Wu, Fangning; Mariga, Alfred Mugambi; Yang, Wenjian; Zhao, Liyan; An, Xinxin; Xin, Zhihong; Yang, Fangmei; Hu, Qiuhui

    2014-12-15

    Button mushroom slices were dehydrated using freeze drying (FD) or FD combined with microwave vacuum drying (FMVD), and the non-volatile component profiles were studied. The results showed that the level of non-volatile components in button mushroom firstly increased during sublimation of FD/FMVD process and then fell during desorption in FD process and MVD in FMVD process. Compared to FD products, the contents of soluble sugars and polyols in FMVD products were relatively low, whereas the contents of total free amino acids were significantly higher, close to the level of fresh mushroom. However, there was no significant difference in the contents of 5'-nucleotides and organic acids between FD and FMVD products. The equivalent umami concentration (EUC) values for FD and FMVD products did not differ from fresh, indicating that both drying methods could effectively preserve MSG (monosodium glutamate)-like components in button mushroom. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Short communication: Effects of vacuum freeze-drying on inactivation of Cronobacter sakazakii ATCC29544 in liquid media with different initial inoculum levels.

    PubMed

    Jiao, Rui; Gao, Jina; Zhang, Xiyan; Zhang, Maofeng; Chen, Jiren; Wu, Qingping; Zhang, Jumei; Ye, Yingwang

    2017-03-01

    Vacuum freeze-drying is an important food-processing technology for valid retention of nutrients and bioactive compounds. Cronobacter sakazakii has been reported to be associated with severe infections in neonates through consumption of contaminated powdered infant formula. In this study, effects of vacuum freeze-drying treatment for 12, 24, and 36 h on inactivation of C. sakazakii with different initial inoculum levels in sterile water, tryptic soy broth (TSB), skim milk, and whole milk were determined. Results indicated that the lethality rate of C. sakazakii in each sample increased with the extension of vacuum freeze-drying time. With initial inoculum levels of 10 2 and 10 3 cfu/mL, the survival of C. sakazakii in different liquid media was significantly affected by vacuum freeze-drying for 12, 24, and 36 h. In addition, the lethality rates of C. sakazakii in whole milk, skim milk, and TSB was significantly reduced compared with those in sterile water. Furthermore, whole milk showed the strongest protective role for C. sakazakii cells, followed by skim milk and TSB medium. Using the scanning electron microscope, the intracellular damage and obvious distortion of C. sakazakii cells were observed after vacuum freeze-drying for 24 and 36 h compared with the untreated sample, and the injured cells increased with the extension of vacuum-drying time. We concluded that inactivation of vacuum freeze-drying on C. sakazakii cells is related to the food matrix, and a combination with other methods for inactivating C. sakazakii is required for ensuring microbial safety of powdered infant formula. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Freeze drying apparatus

    DOEpatents

    Coppa, Nicholas V.; Stewart, Paul; Renzi, Ernesto

    2001-01-01

    The present invention provides methods and apparatus for freeze drying in which a solution, which can be a radioactive salt dissolved within an acid, is frozen into a solid on vertical plates provided within a freeze drying chamber. The solid is sublimated into vapor and condensed in a cold condenser positioned above the freeze drying chamber and connected thereto by a conduit. The vertical positioning of the cold condenser relative to the freeze dryer helps to help prevent substances such as radioactive materials separated from the solution from contaminating the cold condenser. Additionally, the system can be charged with an inert gas to produce a down rush of gas into the freeze drying chamber to also help prevent such substances from contaminating the cold condenser.

  10. Freeze drying method

    DOEpatents

    Coppa, Nicholas V.; Stewart, Paul; Renzi, Ernesto

    1999-01-01

    The present invention provides methods and apparatus for freeze drying in which a solution, which can be a radioactive salt dissolved within an acid, is frozen into a solid on vertical plates provided within a freeze drying chamber. The solid is sublimated into vapor and condensed in a cold condenser positioned above the freeze drying chamber and connected thereto by a conduit. The vertical positioning of the cold condenser relative to the freeze dryer helps to help prevent substances such as radioactive materials separated from the solution from contaminating the cold condenser. Additionally, the system can be charged with an inert gas to produce a down rush of gas into the freeze drying chamber to also help prevent such substances from contaminating the cold condenser.

  11. Effect of drying methods (microwave vacuum, freeze, hot air and sun drying) on physical, chemical and nutritional attributes of five pepper (Capsicum annuum var. annuum) cultivars.

    PubMed

    Maurya, Vaibhav Kumar; Gothandam, Kodiveri Muthukaliannan; Ranjan, Vijay; Shakya, Amita; Pareek, Sunil

    2018-07-01

    A randomized block design experiment was performed to investigate the influence of drying on the physical, chemical and nutritional quality attributes of five prominent cultivars of India under sun drying (SD) (mean temperature 35.5 °C, average daily radiation 5.26 kW h m -2 and mean relative humidity 73.66% RH), hot air drying (HD) at 65 °C, microwave vacuum drying (MVD) (800 W, 5 kPa) and freeze drying (FD) (-50 °C, 5 kPa). Water activity, pH, total phenolic content (TPC), ascorbic acid (AA), capsaicin, β-carotene, color and Scoville heat unit were studied. TPC, AA, capsaicin content, β-carotene, color and water activity were significantly affected by the drying method. FD was observed to be most efficient in minimizing the loss of color, capsaicin and β-carotene. The hotness of analyzed samples decreased in the order 'Bird's Eye' > 'Sannam S4' > 'CO-4' > 'PLR-1' > 'PKM-1' among the studied cultivars, and FD > MVD > HD > SD among the drying methods. The FD method was observed to be the most efficient drying method for retaining capsaicin content over other drying methods (SD, HD, MVD), whereas MVD was found to be most efficient in minimizing the loss to nutritional attributes for all five pepper cultivars. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  12. Vacuum Freeze-Drying, a Method Used To Salvage Water-Damaged Archival and Library Materials: A RAMP Study with Guidelines.

    ERIC Educational Resources Information Center

    McCleary, John M.

    This Records and Archives Management Programme (RAMP) study covers the conservation of archival documents and the application of freeze-drying to the salvage of documents damaged by flood. Following an introductory discussion of the hazards of water, the study presents a broad summary of data on freeze-drying, including the behavior of…

  13. Fundamentals of freeze-drying.

    PubMed

    Nail, Steven L; Jiang, Shan; Chongprasert, Suchart; Knopp, Shawn A

    2002-01-01

    Given the increasing importance of reducing development time for new pharmaceutical products, formulation and process development scientists must continually look for ways to "work smarter, not harder." Within the product development arena, this means reducing the amount of trial and error empiricism in arriving at a formulation and identification of processing conditions which will result in a quality final dosage form. Characterization of the freezing behavior of the intended formulation is necessary for developing processing conditions which will result in the shortest drying time while maintaining all critical quality attributes of the freeze-dried product. Analysis of frozen systems was discussed in detail, particularly with respect to the glass transition as the physical event underlying collapse during freeze-drying, eutectic mixture formation, and crystallization events upon warming of frozen systems. Experiments to determine how freezing and freeze-drying behavior is affected by changes in the composition of the formulation are often useful in establishing the "robustness" of a formulation. It is not uncommon for seemingly subtle changes in composition of the formulation, such as a change in formulation pH, buffer salt, drug concentration, or an additional excipient, to result in striking differences in freezing and freeze-drying behavior. With regard to selecting a formulation, it is wise to keep the formulation as simple as possible. If a buffer is needed, a minimum concentration should be used. The same principle applies to added salts: If used at all, the concentration should be kept to a minimum. For many proteins a combination of an amorphous excipient, such as a disaccharide, and a crystallizing excipient, such as glycine, will result in a suitable combination of chemical stability and physical stability of the freeze-dried solid. Concepts of heat and mass transfer are valuable in rational design of processing conditions. Heat transfer by conduction

  14. Development of freeze dried vegetables

    NASA Technical Reports Server (NTRS)

    Larson, R. W.

    1970-01-01

    The development of freeze dried vegetables to be used in the Apollo food system is discussed. After the initial selection and screening of vegetables, several types of freeze dried vegetables were prepared in small batches. From these small batches, two vegetables were judged satisfactory for further testing and evaluation. These vegetables, mashed potatoes and asparagus, were subjected to storage at 100 deg plus or minus 5 F. for two weeks and then taste tested. The vegetables were also tested to determine if they complied with the microbiological requirements for Apollo food. The space food prototype production guide for the vegetables is submitted.

  15. Freeze-drying of yeast cultures.

    PubMed

    Bond, Chris

    2007-01-01

    A method is described that allows yeast species to be stored using a variation on the standard freeze-drying method, which employs evaporative cooling in a two-stage process. Yeast cultures are placed in glass ampoules after having been mixed with a lyoprotectant. Primary drying is carried out using a centrifuge head connected to a standard freeze-dryer. Once the centrifuge head is running, air is removed and evaporated liquid is captured in the freeze-dryer. Centrifugation continues for 15 min and primary drying for a further 3 h. The ampoules are constricted using a glass blowing torch. They are then placed on the freeze-dryer manifold for secondary drying under vacuum overnight, using phosphorus pentoxide as a desiccant. The ampoules are sealed and removed from the manifold by melting the constricted section. Although the process causes an initial large drop in viability, further losses after storage are minimal. Yeast strains have remained viable for more than 30 yr when stored using this method and sufficient cells are recovered to produce new working stocks. Although survival rates are strain specific, nearly all National Collection of Yeast Cultures strains covering most yeast genera, have been successfully stored with little or no detectable change in strain characteristics.

  16. Mechanisms of deterioration of nutrients. [of freeze dried foods

    NASA Technical Reports Server (NTRS)

    Karel, M.; Flink, J. M.

    1976-01-01

    Methods which produce freeze dried foods of improved quality were examined with emphasis on storage stability. Specific topics discussed include: microstructure of freeze dried systems, investigation of structural changes in freeze dried systems, artificial food matrices, osmotic preconcentration to yield improved quality freeze dried fruits, and storage stability of osmotically preconcentrated freeze dried fruits.

  17. Freeze-dried spermatozoa: A future tool?

    PubMed

    Olaciregui, M; Gil, L

    2017-04-01

    Cryopreservation has been routinely used to preserve sperm of human and different animal species. However, frozen sperm storage for a long time brings many inconveniences because of liquid nitrogen. Many attempts have been made to overcome the disadvantages of the current cryopreservation method. Freeze-drying has been proposed as alternative method for sperm preservation to achieve the ability to store sperm doses indefinitely at ambient temperature or in ordinary refrigerators. At present, it has been reported successfully sperm freeze-drying on many animal species including canine and feline. It is well known that during freeze-drying process, sperm DNA could be damaged, but if suitable protection is provided, the sperm nucleus could preserve the ability to activate the oocyte and embryos could be generated by intracytoplasmic sperm injection (ICSI). Many factors influence the freeze-drying efficacy, so current researches have been conducted to find strategies to control these factors to maintain the sperm DNA integrity. This review describes the latest method of sperm freeze-drying for practical application in preserving and transporting genetic resources. In addition, the approaches to improve the efficiency of the technique were studied. We demonstrated that the DNA integrity of freeze-dried dog sperm is affected by the composition of the freeze-drying solution as well as the temperature and period of storage. Further studies are necessary to refine freeze-drying protocol in order to protect the DNA and maintain the sperm functionality and obtain offspring from freeze-dried sperm. © 2016 Blackwell Verlag GmbH.

  18. Suitability of microwave drying for mealworms (Tenebrio molitor) as alternative to freeze drying: Impact on nutritional quality and colour.

    PubMed

    Lenaerts, S; Van Der Borght, M; Callens, A; Van Campenhout, L

    2018-07-15

    Freeze drying represents the current practice to stabilize mealworms, even though it is an energy demanding technique. Therefore, it was examined in the present study whether microwave drying could be a proper alternative. To this end, the impact of both drying techniques on the proximate composition, vitamin B 12 content, fatty acid profile, oxidation status and colour parameters of mealworms was investigated. Furthermore, the influence of the application of vacuum during microwave drying was studied. The different drying technologies resulted in small differences in the proximate composition, while the vitamin B 12 content was only reduced by microwave drying. The fat fraction of freeze dried mealworms showed a higher oxidation status than the fat of microwave dried mealworms. Application of a vacuum during the microwave drying process did not appear to offer advantages. This research shows that for mealworms microwave drying can be a proper alternative to freeze drying. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Pharmaceutical patent applications in freeze-drying.

    PubMed

    Ekenlebie, Edmond; Einfalt, Tomaž; Karytinos, Arianna Irò; Ingham, Andrew

    2016-09-01

    Injectable products are often the formulation of choice for new therapeutics; however, formulation in liquids often enhances degradation through hydrolysis. Thus, freeze-drying (lyophilization) is regularly used in pharmaceutical manufacture to reduce water activity. Here we examine its contribution to 'state of the art' and look at its future potential uses. A comprehensive search of patent databases was conducted to characterize the international patent landscape and trends in the use of freeze-drying. A total of 914 disclosures related to freeze-drying, lyophilization or drying of solid systems in pressures and temperatures equivalent to those of freeze-drying were considered over the period of 1992-2014. Current applications of sublimation technology were contrasted across two periods those with patents due to expire (1992-1993) and those currently filed. The number of freeze-drying technology patents has stabilized after initial activity across the biotechnology sector in 2011 and 2012. Alongside an increasing trend for patent submissions, freeze-drying submissions have slowed since 2002 and is indicative of a level of maturity.

  20. Encapsulation of black carrot juice using spray and freeze drying.

    PubMed

    Murali, S; Kar, Abhijit; Mohapatra, Debabandya; Kalia, Pritam

    2015-12-01

    Black carrot juice extracted using pectinase enzyme was encapsulated in three different carrier materials (maltodextrin 20DE, gum arabic and tapioca starch) using spray drying at four inlet temperatures (150, 175, 200 and 225 ℃) and freeze drying at a constant temperature of - 53 ℃ and vacuum of 0.22-0.11 mbar with the constant feed mixture. The products were analyzed for total anthocyanin content, antioxidant activity, water solubility index, encapsulation efficiency and total colour change. For both the drying methods followed in this study, maltodextrin 20DE as the carrier material has proven to be better in retaining maximum anthocyanin and antioxidant activity compared to gum arabic and tapioca starch. The best spray dried product, was obtained at 150 ℃. The most acceptable was the freeze dried product with maximum anthocyanin content, antioxidant activity, water solubility index, encapsulation efficiency and colour change. © The Author(s) 2014.

  1. Freeze-drying of lactic acid bacteria.

    PubMed

    Fonseca, Fernanda; Cenard, Stéphanie; Passot, Stéphanie

    2015-01-01

    Lactic acid bacteria are of great importance for the food and biotechnology industry. They are widely used as starters for manufacturing food (e.g., yogurt, cheese, fermented meats, and vegetables) and probiotic products, as well as for green chemistry applications. Freeze-drying or lyophilization is a convenient method for preservation of bacteria. By reducing water activity to values below 0.2, it allows long-term storage and low-cost distribution at suprazero temperatures, while minimizing losses in viability and functionality. Stabilization of bacteria via freeze-drying starts with the addition of a protectant solution to the bacterial suspension. Freeze-drying includes three steps, namely, (1) freezing of the concentrated and protected cell suspension, (2) primary drying to remove ice by sublimation, and (3) secondary drying to remove unfrozen water by desorption. In this chapter we describe a method for freeze-drying of lactic acid bacteria at a pilot scale, thus allowing control of the process parameters for maximal survival and functionality recovery.

  2. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG

    PubMed Central

    ten Have, R.; Reubsaet, K.; van Herpen, P.; Kersten, G.; Amorij, J.-P.

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG. PMID:26981867

  3. Demonstrating Functional Equivalence of Pilot and Production Scale Freeze-Drying of BCG.

    PubMed

    Ten Have, R; Reubsaet, K; van Herpen, P; Kersten, G; Amorij, J-P

    2016-01-01

    Process analytical technology (PAT)-tools were used to monitor freeze-drying of Bacille Calmette-Guérin (BCG) at pilot and production scale. Among the evaluated PAT-tools, there is the novel use of the vacuum valve open/close frequency for determining the endpoint of primary drying at production scale. The duration of primary drying, the BCG survival rate, and the residual moisture content (RMC) were evaluated using two different freeze-drying protocols and were found to be independent of the freeze-dryer scale evidencing functional equivalence. The absence of an effect of the freeze-dryer scale on the process underlines the feasibility of the pilot scale freeze-dryer for further BCG freeze-drying process optimization which may be carried out using a medium without BCG.

  4. Preservation of flavor in freeze dried green beans

    NASA Technical Reports Server (NTRS)

    Huber, C. S.; Heidelbaugh, N. D.; Davis, D.

    1973-01-01

    Before freeze drying, green beans are heated to point at which their cell structure is altered. Beans freeze dried with altered cell structure have improved rehydration properties and retain color, flavor, and texture.

  5. Retention of antioxidant capacity of vacuum microwave dried cranberry.

    PubMed

    Leusink, Gwen J; Kitts, David D; Yaghmaee, Parastoo; Durance, Tim

    2010-04-01

    In this study, cranberries were dried by vacuum-microwave drying (VMD), freeze-drying (FD), or hot air-drying (AD), to compare the effects of different drying processes on both physical changes as well as the retention of bioactive components in dried samples. Total porosity (%) and average pore radius of dehydrated cranberries were greater using VMD compared to FD and AD (P < 0.05). Crude methanol cranberry powdered extracts were fractionated by solid phase extraction (SPE) into organic acid-, total phenolics-, anthocyanin-, or proanthocyanidin-enriched extracts, respectively. The chemical composition of the 60% acidified methanol fractions contained cyanidin-3-galactoside, cyanidin-3-arabinoside, peonidin-3-galactoside, and peonidin-3-arabinoside, as assessed by HPLC. Antioxidant activities of cranberry fractions were measured using chemical ORAC and ABTS methods. The 60% acidified methanol fraction had a significantly higher (P < 0.05) antioxidant potential than the other chemical fractions, which was largely attributed to the relatively higher anthocyanin content. In general, vacuum-microwave drying and freeze-drying resulted in similar retention of anthocyanins and antioxidant activity, which were both relatively higher (P < 0.05) than that recovered from cranberries dried by hot air drying.

  6. Non-Caking Freeze Dried Applesauce

    DTIC Science & Technology

    A study was initiated to develop an applesauce which resists caking when subjected to elevated temperatures such as 37.7C. for two weeks and/or 57C...following results were obtained: (1) The degree of caking of the freeze dried applesauce powder was correlated with the amount of juice extracted. (2... applesauce powders. (3) Reducing sugars appear to be the factor contributing most significantly to the caking with the higher reducing sugar levels producing the higher degrees of caking.

  7. Characteristics of sugar surfactants in stabilizing proteins during freeze-thawing and freeze-drying.

    PubMed

    Imamura, Koreyoshi; Murai, Katsuyuki; Korehisa, Tamayo; Shimizu, Noriyuki; Yamahira, Ryo; Matsuura, Tsutashi; Tada, Hiroko; Imanaka, Hiroyuki; Ishida, Naoyuki; Nakanishi, Kazuhiro

    2014-06-01

    Sugar surfactants with different alkyl chain lengths and sugar head groups were compared for their protein-stabilizing effect during freeze-thawing and freeze-drying. Six enzymes, different in terms of tolerance against inactivation because of freeze-thawing and freeze-drying, were used as model proteins. The enzyme activities that remained after freeze-thawing and freeze-drying in the presence of a sugar surfactant were measured for different types and concentrations of sugar surfactants. Sugar surfactants stabilized all of the tested enzymes both during freeze-thawing and freeze-drying, and a one or two order higher amount of added sugar surfactant was required for achieving protein stabilization during freeze-drying than for the cryoprotection. The comprehensive comparison showed that the C10-C12 esters of sucrose or trehalose were the most effective through the freeze-drying process: the remaining enzyme activities after freeze-thawing and freeze-drying increased at the sugar ester concentrations of 1-10 and 10-100 μM, respectively, and increased to a greater extent than for the other surfactants at higher concentrations. Results also indicate that, when a decent amount of sugar was also added, the protein-stabilizing effect of a small amount of sugar ester through the freeze-drying process could be enhanced. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Modification of physical properties of freeze-dried rice

    NASA Technical Reports Server (NTRS)

    Huber, C. S.

    1971-01-01

    Freeze cycling process consists of alternately freezing and thawing precooked rice for two cycles, rice is then frozen and freeze-dehydrated in vacuum sufficient to remove water from rice by sublimitation. Process modifies rice grain structure and porosity, enabling complete rehydration in one minute in hot water.

  9. Influence of the Ultrasonic Power Applied on Freeze Drying Kinetics

    NASA Astrophysics Data System (ADS)

    Brines, C.; Mulet, A.; García-Pérez, J. V.; Riera, E.; Cárcel, J. A.

    The atmospheric freeze drying (AFD) constitutes an interesting alternative to vacuum freeze drying providing products with similar quality at lowest cost. However, the long process time needed represent an important drawback. In this sense, the application of high intensity ultrasound can enhance heat and mass transfer and intensify the operation. In hot air drying operation, the ultrasonic effects are dependent on the process variables such as air velocity, internal sample structure or ultrasonic power applied. However, in AFD processes, the internal structure of material or the air velocity has not significant influence on the magnitude of ultrasonic effects. The aim of this work was to determine the influence on drying kinetics of the ultrasonic power applied during the AFD of apple. For that purpose, AFD experiments (-10 °C, 2 m/s and 15% relative humidity) of apple slabs (cv. Granny Smith, 30 x 30 x 10 mm) were carried out with ultrasound application (21 kHz) at different power levels (0, 10.3, 20.5 and 30.8 kW/m3). The drying kinetics was obtained from the initial moisture content and the weight evolution of samples during drying. Experimental results showed a significant (p<0.05) influence of the ultrasound application on drying. Thus, drying time was shorter as higher the ultrasonic power applied. From modeling, it was observed that the effective diffusion coefficient identified was 4.8 times higher when ultrasound was applied at the lowest power tested (10.3 kW/m3) that illustrated the high intensification potential of ultrasound application in the AFD.

  10. Drying a tuberculosis vaccine without freezing.

    PubMed

    Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R; Edwards, David

    2007-02-20

    With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.

  11. References on Compression of Freeze-Dried Foods

    DTIC Science & Technology

    1978-08-01

    ready-to-eat, freeze-dried scrambled egg . Swift and Co., Contract No. DA 19- 129-AMC-121. 67-49-FD (FD-54). January 1967 (AD 650637). In the design...significantly poorer in organoleptic properties than from grades A and B eggs. Freeze- dried scrambled egg packed in cans kept better in storage than when...scrambled, cooked, freeze-dried whole egg product was developed which possessed the appearance, aroma, flavor and texture similar to pan- fried scrambled

  12. Limonene encapsulation in freeze dried gellan systems.

    PubMed

    Evageliou, Vasiliki; Saliari, Dimitra

    2017-05-15

    The encapsulation of limonene in freeze-dried gellan systems was investigated. Surface and encapsulated limonene content was determined by measurement of the absorbance at 252nm. Gellan matrices were both gels and solutions. For a standard gellan concentration (0.5wt%) gelation was induced by potassium or calcium chloride. Furthermore, gellan solutions of varying concentrations (0.25-1wt%) were also studied. Limonene was added at two different concentrations (1 and 2mL/100g sample). Gellan gels encapsulated greater amounts of limonene than solutions. Among all gellan gels, the KCl gels had the greater encapsulated limonene content. However, when the concentration of limonene was doubled in these KCl gels, the encapsulated limonene decreased. The surface limonene content was significant, especially for gellan solutions. The experimental conditions and not the mechanical properties of the matrices were the dominant factor in the interpretation of the observed results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Effects of stepwise dry/wet-aging and freezing on meat quality of beef loins.

    PubMed

    Kim, Yuan H Brad; Meyers, Brandon; Kim, Hyun-Wook; Liceaga, Andrea M; Lemenager, Ronald P

    2017-01-01

    The objective of this study was to evaluate the effects of stepwise dry/wet-aging and freezing method on quality attributes of beef loins. Paired loins (M. Longissimus lumborum) from eight carcasses were assigned to either stepwise dry/wet-aging (carcass dry-aging for 10days then further wet-aging for 7days in vacuum bags) or carcass dry-aging only for 17days. Then, each loin was divided into three sections for freezing (never-frozen, blast or cryogenic freezing). Stepwise dry/wet-aged loin had lower purge/drip loss and shear force than conventionally dry-aged loin (P<0.05), but similar color and sensory characteristics (P>0.05). The cryogenic freezing resulted in a significant decrease in shear force values and a significant improvement in water-holding capacity (WHC). These findings indicate that the stepwise dry/wet-aging coupled with cryogenic freezing could provide beneficial impacts to the local meat industry by providing equivalent quality attributes as conventional dry-aging and improving WHC of frozen/thawed meat, while reducing the time needed for dry-aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Assessing storage of stability and mercury reduction of freeze-dried Pseudomonas putida within different types of lyoprotectant

    NASA Astrophysics Data System (ADS)

    Azoddein, Abdul Aziz Mohd; Nuratri, Yana; Azli, Faten Ahada Mohd; Bustary, Ahmad Bazli

    2017-12-01

    Pseudomonas putida is a potential strain in biological treatment to remove mercury contained in the effluent of petrochemical industry due to its mercury reductase enzyme that able to reduce ionic mercury to elementary mercury. Freeze-dried P. putida allows easy, inexpensive shipping, handling and high stability of the product. This study was aimed to freeze dry P. putida cells with addition of lyoprotectant. Lyoprotectant was added into the cells suspension prior to freezing. Dried P. putida obtained was then mixed with synthetic mercury. Viability of recovery P. putida after freeze dry was significantly influenced by the type of lyoprotectant. Among the lyoprotectants, tween 80/ sucrose was found to be the best lyoprotectant. Sucrose was able to recover more than 78% (6.2E+09 CFU/ml) of the original cells (7.90E+09CFU/ml) after freeze dry and able to retain 5.40E+05 viable cells after 4 weeks storage at 4 °C without vacuum. Polyethylene glycol (PEG) pre-treated freeze dried cells and broth pre-treated freeze dried cells after the freeze-dry process recovered more than 64% (5.0 E+09CFU/ml) and >0.1% (5.60E+07CFU/ml). Freeze-dried P. putida cells in PEG and broth cannot survive after 4 weeks storage. Freeze dry also does not really change the pattern of growth P. putida but extension of lag time was found 1 hour after 3 weeks of storage. Additional time was required for freeze-dried P. putida cells to recover before introducing freeze-dried cells to more complicated condition such as mercury solution. The maximum mercury reduction of PEG pre-treated freeze-dried cells after freeze dry and after storage of 3 weeks was 17.91 %. The maximum of mercury reduction of tween 80/sucrose pre-treated freeze-dried cells after freeze dry and after storage 3 weeks was 25.03%. Freeze dried P. putida was found to have lower mercury reduction compare to the fresh P. putida that has been grown in agar. Result from this study may be beneficial and useful as initial reference before

  15. Preparation of High-Grade Powders from Tomato Paste Using a Vacuum Foam Drying Method.

    PubMed

    Sramek, Martin; Schweiggert, Ralf Martin; van Kampen, Andreas; Carle, Reinhold; Kohlus, Reinhard

    2015-08-01

    We present a rapid and gentle drying method for the production of high-grade tomato powders from double concentrated tomato paste, comparing results with powders obtained by foam mat air drying and freeze dried powders. The principle of this method consists of drying tomato paste in foamed state at low temperatures in vacuum. The formulations were dried at temperatures of 50, 60, and 70 °C and vacuum of 200 mbar. Foam stability was affected by low serum viscosity and the presence of solid particles in tomato paste. Consequently, serum viscosity was increased by maltodextrin addition, yielding optimum stability at tomato paste:maltodextrin ratio of 2.4:1 (w/w) in dry matter. Material foamability was improved by addition of 0.5% (w/w, fresh weight) egg white. Because of solid particles in tomato paste, foam air filling had to be limited to critical air volume fraction of Φ = 0.7. The paste was first pre-foamed to Φ = 0.2 and subsequently expanded in vacuo. After drying to a moisture content of 5.6% to 7.5% wet base (w.b.), the materials obtained were in glassy state. Qualities of the resulting powders were compared with those produced by freeze and air drying. Total color changes were the least after vacuum drying, whereas air drying resulted in noticeable color changes. Vacuum foam drying at 50 °C led to insignificant carotenoid losses, being equivalent to the time-consuming freeze drying method. In contrast, air drying caused lycopene and β-carotene losses of 18% to 33% and 14% to 19% respectively. Thus, vacuum foam drying enables production of high-grade tomato powders being qualitatively similar to powders obtained by freeze drying. © 2015 Institute of Food Technologists®

  16. Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses.

    PubMed

    De Meyer, L; Van Bockstal, P-J; Corver, J; Vervaet, C; Remon, J P; De Beer, T

    2015-12-30

    Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its impact on total drying time. Five different formulations, each having a different dry cake resistance, were tested. After freezing, the traditionally frozen vials were placed on the shelves while the spin-frozen vials were placed in aluminum vial holders providing radial energy supply during drying. Different primary drying conditions and chamber pressures were evaluated. After 2h of primary drying, the amount of sublimed ice was determined in each vial. Each formulation was monitored in-line using NIR spectroscopy during drying to determine the sublimation endpoint and the influence of drying conditions upon total drying time. For all tested formulations and applied freeze-drying conditions, there was a significant higher sublimation rate in the spin-frozen vials. This can be explained by the larger product surface and the lower importance of product resistance because of the much thinner product layers in the spin frozen vials. The in-line NIR measurements allowed evaluating the influence of applied drying conditions on the drying trajectories. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Wet/Dry Vacuum Cleaner

    NASA Technical Reports Server (NTRS)

    Reimers, Harold; Andampour, Jay; Kunitser, Craig; Thomas, Ike

    1995-01-01

    Vacuum cleaner collects and retains dust, wet debris, and liquids. Designed for housekeeping on Space Station Freedom, it functions equally well in normal Earth Gravity or in microgravity. Generates acoustic noise at comfortably low levels and includes circuitry that reduces electromagnetic interference to other electronic equipment. Draws materials into bag made of hydrophobic sheet with layers of hydrophilic super-absorbing pads at downstream end material. Hydrophilic material can gel many times its own weight of liquid. Blower also provides secondary airflow to cool its electronic components.

  18. Freeze-drying process design by manometric temperature measurement: design of a smart freeze-dryer.

    PubMed

    Tang, Xiaolin Charlie; Nail, Steven L; Pikal, Michael J

    2005-04-01

    To develop a procedure based on manometric temperature measurement (MTM) and an expert system for good practices in freeze drying that will allow development of an optimized freeze-drying process during a single laboratory freeze-drying experiment. Freeze drying was performed with a FTS Dura-Stop/Dura-Top freeze dryer with the manometric temperature measurement software installed. Five percent solutions of glycine, sucrose, or mannitol with 2 ml to 4 ml fill in 5 ml vials were used, with all vials loaded on one shelf. Details of freezing, optimization of chamber pressure, target product temperature, and some aspects of secondary drying are determined by the expert system algorithms. MTM measurements were used to select the optimum shelf temperature, to determine drying end points, and to evaluate residual moisture content in real-time. MTM measurements were made at 1 hour or half-hour intervals during primary drying and secondary drying, with a data collection frequency of 4 points per second. The improved MTM equations were fit to pressure-time data generated by the MTM procedure using Microcal Origin software to obtain product temperature and dry layer resistance. Using heat and mass transfer theory, the MTM results were used to evaluate mass and heat transfer rates and to estimate the shelf temperature required to maintain the target product temperature. MTM product dry layer resistance is accurate until about two-thirds of total primary drying time is over, and the MTM product temperature is normally accurate almost to the end of primary drying provided that effective thermal shielding is used in the freeze-drying process. The primary drying times can be accurately estimated from mass transfer rates calculated very early in the run, and we find the target product temperature can be achieved and maintained with only a few adjustments of shelf temperature. The freeze-dryer overload conditions can be estimated by calculation of heat/mass flow at the target product

  19. Design of freeze-drying processes for pharmaceuticals: practical advice.

    PubMed

    Tang, Xiaolin; Pikal, Michael J

    2004-02-01

    Design of freeze-drying processes is often approached with a "trial and error" experimental plan or, worse yet, the protocol used in the first laboratory run is adopted without further attempts at optimization. Consequently, commercial freeze-drying processes are often neither robust nor efficient. It is our thesis that design of an "optimized" freeze-drying process is not particularly difficult for most products, as long as some simple rules based on well-accepted scientific principles are followed. It is the purpose of this review to discuss the scientific foundations of the freeze-drying process design and then to consolidate these principles into a set of guidelines for rational process design and optimization. General advice is given concerning common stability issues with proteins, but unusual and difficult stability issues are beyond the scope of this review. Control of ice nucleation and crystallization during the freezing step is discussed, and the impact of freezing on the rest of the process and final product quality is reviewed. Representative freezing protocols are presented. The significance of the collapse temperature and the thermal transition, denoted Tg', are discussed, and procedures for the selection of the "target product temperature" for primary drying are presented. Furthermore, guidelines are given for selection of the optimal shelf temperature and chamber pressure settings required to achieve the target product temperature without thermal and/or mass transfer overload of the freeze dryer. Finally, guidelines and "rules" for optimization of secondary drying and representative secondary drying protocols are presented.

  20. Optimum Parameters for Freeze-Drying Decellularized Arterial Scaffolds

    PubMed Central

    Sheridan, William S.; Duffy, Garry P.

    2013-01-01

    Decellularized arterial scaffolds have achieved success in advancing toward clinical use as vascular grafts. However, concerns remain regarding long-term preservation and sterilization of these scaffolds. Freeze drying offers a means of overcoming these concerns. In this study, we investigated the effects of various freeze-drying protocols on decellularized porcine carotid arteries and consequently, determined the optimum parameters to fabricate a stable, preserved scaffold with unaltered mechanical properties. Freeze drying by constant slow cooling to two final temperatures ((Tf), −10°C and −40°C) versus instant freezing was investigated by histological examination and mechanical testing. Slow cooling to Tf= −10°C produced a stiffer and less distensible response than the non freeze-dried scaffolds and resulted in disruption to the collagen fibers. The mechanical response of Tf= −40°C scaffolds demonstrated disruption to the elastin network, which was confirmed with histology. Snap freezing scaffolds in liquid nitrogen and freeze drying to Tf= −40°C with a precooled shelf at −60°C produced scaffolds with unaltered mechanical properties and a histology resembling non-freeze-dried scaffolds. The results of this study demonstrate the importance of optimizing the nucleation and ice crystal growth/size to ensure homogenous drying, preventing extracellular matrix disruption and subsequent inferior mechanical properties. This new manufacturing protocol creates the means for the preservation and sterilization of decellularized arterial scaffolds while simultaneously maintaining the mechanical properties of the tissue. PMID:23614758

  1. New Processes for Freeze-Drying in Dual-Chamber Systems.

    PubMed

    Werk, T; Ludwig, I S; Luemkemann, J; Huwyler, J; Mahler, H-C; Haeuser, C R; Hafner, M

    2016-01-01

    Dual-chamber systems can offer self-administration and home care use for lyophilized biologics. Only a few products have been launched in dual-chamber systems so far-presumably due to dual-chamber systems' complex and costly drug product manufacturing process. Within this paper, two improved processes (both based on tray filling technology) for freeze-drying pharmaceuticals in dual-chamber systems are described. Challenges with regards to heat transfer were tackled by (1) performing the freeze-drying step in a needle-down orientation in combination with an aluminum block, or (2) freeze-drying the drug product "externally" in a metal cartridge with subsequent filling of the lyophilized cake into the dual-chamber system. Metal-mediated heat transfer was shown to be efficient in both cases and batch (unit-to-unit) homogeneity with regards to sublimation rate was increased. It was difficult to influence ice crystal size using different methods when in use with an aluminum block due to its heat capacity. Using such a metal carrier implies a large heat capacity leading to relatively small ice crystals. Compared to the established process, drying times were reduced by half using the new processes. The drying time was, however, longer for syringes compared to vials due to the syringe design (long and slim). The differences in drying times were less pronounced for aggressive drying cycles. The proposed processes may help to considerably decrease investment costs into dual-chamber system fill-finish equipment. Dual-chamber syringes offer self-administration and home care use for freeze-dried pharmaceuticals. Only a few products have been launched in dual-chamber syringes so far-presumably due to their complex and costly drug product manufacturing process. In this paper two improved processes for freeze-drying pharmaceuticals in dual-chamber syringes are described. The major challenge of freeze-drying is to transfer heat through a vacuum. The proposed processes cope with this

  2. Rubber closures for freeze-dried products.

    PubMed

    Hopkins, G H

    1976-10-01

    Once a biological product has been developed to perform its required medical or pharmaceutical function, it is essential that a container-closure system by chosen which will preserve the efficacy of the product up to the point of administration. The general requirements applicable to proper closure function will be reviewed and the suitability of natural and synthetic elastomers to perform these functions will be discussed. The specialized application of elastomeric materials as closures for freeze-dried products presents additional requirements which are superimposed upon those previously discussed. The first of these unique considerations relates to the proper physical design which will permit the outgassing of water vapor during the sublimation step in the lyophilizing chamber. During this outgassing the design must also permit the closure to remain affixed in the neck while only partially inserted. Since these preparations are lyophilized because they are unstable in aqueous solutions, the elastomer used must constitute an effective barrier to the transmission of moisture vapor through the closure. The MVT and gas transmission properties of elastomers will be discussed. Special consideration will be given to the extremely low temperatures used in the sublimation, stoppering, and storage before use of lyophilized products. The phenomenon of glass transition points with different elastomers will be explained as its relation to satisfactory performance of the closure function at low temperatures.

  3. Effects of freezing, freeze drying and convective drying on in vitro gastric digestion of apples.

    PubMed

    Dalmau, Maria Esperanza; Bornhorst, Gail M; Eim, Valeria; Rosselló, Carmen; Simal, Susana

    2017-01-15

    The influence of processing (freezing at -196°C in liquid N2, FN sample; freeze-drying at -50°C and 30Pa, FD sample; and convective drying at 60°C and 2m/s, CD sample) on apple (var. Granny Smith) behavior during in vitro gastric digestion was investigated. Dried apples (FD and CD samples) were rehydrated prior to digestion. Changes in carbohydrate composition, moisture, soluble solids, acidity, total polyphenol content (TPC), and antioxidant activity (AA) of apple samples were measured at different times during digestion. Processing resulted in disruption of the cellular structure during digestion, as observed by scanning electron microscopy, light microscopy, and changes in carbohydrate composition. Moisture content increased (6-11% dmo), while soluble solids (55-78% dmo), acidity (44-72% dmo), total polyphenol content (30-61% dmo), and antioxidant activity (41-87%) decreased in all samples after digestion. Mathematical models (Weibull and exponential models) were used to better evaluate the influence of processing on apple behavior during gastric digestion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Stabilization of Live Attenuated Influenza Vaccines by Freeze Drying, Spray Drying, and Foam Drying.

    PubMed

    Lovalenti, Phillip M; Anderl, Jeff; Yee, Luisa; Nguyen, Van; Ghavami, Behnaz; Ohtake, Satoshi; Saxena, Atul; Voss, Thomas; Truong-Le, Vu

    2016-05-01

    The goal of this research is to develop stable formulations for live attenuated influenza vaccines (LAIV) by employing the drying methods freeze drying, spray drying, and foam drying. Formulated live attenuated Type-A H1N1 and B-strain influenza vaccines with a variety of excipient combinations were dried using one of the three drying methods. Process and storage stability at 4, 25 and 37°C of the LAIV in these formulations was monitored using a TCID50 potency assay. Their immunogenicity was also evaluated in a ferret model. The thermal stability of H1N1 vaccine was significantly enhanced through application of unique formulation combinations and drying processes. Foam dried formulations were as much as an order of magnitude more stable than either spray dried or freeze dried formulations, while exhibiting low process loss and full retention of immunogenicity. Based on long-term stability data, foam dried formulations exhibited a shelf life at 4, 25 and 37°C of >2, 1.5 years and 4.5 months, respectively. Foam dried LAIV Type-B manufactured using the same formulation and process parameters as H1N1 were imparted with a similar level of stability. Foam drying processing methods with appropriate selection of formulation components can produce an order of magnitude improvement in LAIV stability over other drying methods.

  5. Evaluation of Dry, Rough Vacuum Pumps

    NASA Technical Reports Server (NTRS)

    Hunter, Brian

    2006-01-01

    This document provides information on the testing and evaluation of thirteen dry rough vacuum pumps of various designs and from various manufacturers. Several types of rough vacuum pumps were evaluated, including scroll, roots, and diaphragm pumps. Tests included long term testing, speed curve generation, voltage variance, vibrations emissions and susceptibility, electromagnetic interference emissions and susceptibility, static leak rate, exhaust restriction, response/recovery time tests, and a contamination analysis for scroll pumps. Parameters were found for operation with helium, which often is not provided from the manufacturer

  6. Protective effect of sugars on storage stability of microwave freeze-dried and freeze-dried Lactobacillus paracasei F19.

    PubMed

    Ambros, S; Hofer, F; Kulozik, U

    2018-05-31

    Microwave freeze drying in comparison to conventional freeze drying allows for intensification of the preservation process of lactic acid bacteria without imposing additional processing stress. Viability as a function of storage time of microwave freeze-dried Lactobacillus paracasei ssp. paracasei F19 was investigated in comparison to conventionally lyophilized bacteria of the same strain. Further, the impact of the protectants, sorbitol, trehalose and maltodextrin, on shelf life was analyzed. The highest inactivation rates of 0.035 and 0.045 d -1 , respectively, were found for cultures without protectants. Thus, all additives were found to exhibit a protective effect during storage with inactivation rates between 0.015 and 0.040 d -1 . Although trehalose and maltodextrin samples were in the glassy state during storage, in contrast to samples containing sorbitol as protectant, the best protective effect could be found for sorbitol with the lowest inactivation rate of 0.015 d -1 . Due to its low molecular weight, it might protect cells owing to better adsorption to the cytoplasma membrane. Sorbitol additionally shows antioxidative properties. Storage behavior of microwave freeze-dried cultures follows the typical behavior of a product dried by conventional lyophilization. No significant influence of the drying technique on storage behavior was detected. General findings concerning storage behavior in freeze drying are likely to be applicable in microwave freeze drying with only slight adjustments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Freeze-drying of silica nanoparticles: redispersibility toward nanomedicine applications.

    PubMed

    Picco, Agustin S; Ferreira, Larissa F; Liberato, Michelle S; Mondo, Gabriela B; Cardoso, Mateus B

    2018-01-01

    To study freeze-drying of silica nanoparticles (SiO 2 NPs) in order to find suitable conditions to produce lyophilized powders with no aggregation after resuspension and storage. SiO 2 NPs were synthesized using a Stöber-based procedure, and characterized by scanning electron microscopy, dynamic light scattering and nitrogen adsorption/desorption isotherms. SiO 2 NPs hydrodynamic diameters were compared prior and after freeze-drying in the presence/absence of carbohydrate protectants. Glucose was found to be the most suitable protectant against the detrimental effects of lyophilization. The minimum concentration of carbohydrate required to effectively protect SiO 2 NPs from aggregation during freeze-drying is influenced by the nanoparticle's size and texture. Negligible aggregation was observed during storage. Carbohydrates can be used during SiO 2 NPs freeze-drying process to obtain redispersable solids that maintain original sizes without residual aggregation.

  8. [Freeze drying process optimization of ginger juice-adjuvant for Chinese materia medica processing and stability of freeze-dried ginger juice powder].

    PubMed

    Yang, Chun-Yu; Guo, Feng-Qian; Zang, Chen; Cao, Hui; Zhang, Bao-Xian

    2018-02-01

    Ginger juice, a commonly used adjuvant for Chinese materia medica, is applied in processing of multiple Chinese herbal decoction pieces. Because of the raw materials and preparation process of ginger juice, it is difficult to be preserved for a long time, and the dosage of ginger juice in the processing can not be determined base on its content of main compositions. Ginger juice from different sources is hard to achieve consistent effect during the processing of traditional Chinese herbal decoction pieces. Based on the previous studies, the freeze drying of ginger juice under different shelf temperatures and vacuum degrees were studied, and the optimized freeze drying condition of ginger juice was determined. The content determination method for 6-gingerol, 8-gingerol, 10-gingerol and 6-shagaol in ginger juice and redissolved ginger juice was established. The content changes of 6-gingerol, 8-gingerol, 10-gingerol, 6-gingerol, 6-shagaol, volatile oil and total phenol were studied through the drying process and 30 days preservation period. The results showed that the freeze drying time of ginger juice was shortened after process optimization; the compositions basically remained unchanged after freeze drying, and there was no significant changes in the total phenol content and gingerol content, but the volatile oil content was significantly decreased( P <0.05). Within 30 days, the contents of gingerol, total phenol, and volatile oil were on the decline as a whole. This study has preliminarily proved the feasibility of freeze-drying process of ginger juice as an adjuvant for Chinese medicine processing. Copyright© by the Chinese Pharmaceutical Association.

  9. Mechanisms of deterioration of nutrients. [improved quality of freeze-dried foods

    NASA Technical Reports Server (NTRS)

    Karel, M.; Flink, J. M.

    1978-01-01

    Methods for improving the quality of freeze-dried foods were investigated. Areas discussed include: (1) microstructure of freeze-dried systems, (2) structural changes in freeze-dried systems, (3) artificial food matrices, and (4) osmotic preconcentration to yield improved freeze-dried products.

  10. Freeze-dried dog sperm: Dynamics of DNA integrity.

    PubMed

    Olaciregui, M; Luño, V; Gonzalez, N; De Blas, I; Gil, L

    2015-10-01

    Freeze-drying (FD) has been proposed as an alternative method to preserve spermatozoa. During the FD procedure, sperm DNA might become damaged by both freezing and drying stresses caused by the endonucleases, the oxidative stress and the storage conditions. We examined the DNA integrity of dog sperm freeze-dried with two kinds of chelating agents in FD buffers and storage at two different temperatures. Ejaculated sperm from four dogs were suspended in basic medium (10 mM Tris-HCl buffer+50 mM NaCl) supplemented with 50 mM EGTA or with 50 mM EDTA and then freeze-dried. Sperm samples were stored at 4°C as room temperature, and the analysis of DNA damage was performed after a month and 5 months of storage using a Sperm Chromatin Dispersion test. We found four different sperm populations according to the size of the halos around the sperm head: (1) absent halo, (2) <6 μm, (3) 6-10 μm, (4) >10 μm. All of them coexisted in each freeze-dried dog semen samples and differed significantly among different treatments. The highest percentage of spermatozoa with halo >10 μm was obtained when the semen samples were freeze-dried in EDTA medium and stored at room temperature for five months. Results suggested that both, the kind of chelating agent as well as storage temperature and period, influenced DNA integrity of freeze-dried dog sperm. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Freeze Drying of Fruits and Vegetables: A Laboratory Experiment.

    ERIC Educational Resources Information Center

    Noble, Richard D.

    1979-01-01

    Describes a laboratory experiment for freeze-drying fruits and vegetables which aims to expose college students to the principles of drying and simultaneous heat and mass transfer. The experimental apparatus, procedure of the experiment, and data analysis are also included. (HM)

  12. High post-thaw survival of ram sperm after partial freeze-drying.

    PubMed

    Arav, Amir; Idda, Antonella; Nieddu, Stefano Mario; Natan, Yehudit; Ledda, Sergio

    2018-03-14

    Recrystallization damages occur when a frozen sample is held at high subzero temperatures and when the warming process is too slow. In this work, ram semen diluted in two different concentrations of sugar solutions (Lyo A consisted of 0.4 M sorbitol and 0.25 M trehalose, and the second, Lyo B composed of 0.26 M sorbitol and 0.165 M trehalose) in egg yolk and Tris medium were compared after freezing 10 μL samples to: (1) - 10, - 25, and - 35 °C and thawing. (2) Freezing to - 10 and - 25 °C, holding for 1 h and then thawing, and (3) freezing to - 10 and - 25 °C and drying for 1 h at these temperatures at a vacuum of 80 mTorr, prior thawing. For drying, we used a new freeze-drying apparatus (Darya, FertileSafe, Israel) having a condensation temperature below - 110 °C and a vacuum pressure of 10-100 mTorr that is reached in less than 10s. Results showed that samples in Lyo B solution frozen at - 25 °C had significantly higher sperm motility in partially freeze-dried samples than frozen samples (46.6 ± 2.8% vs 1.2 ± 2.5%, P < 0.001). Moreover, partially dried samples in Lyo B showed higher motility than Lyo A at - 25 °C (46.6 ± 2.8% vs 35 ± 4%). Cryomicroscopy and low-temperature/low-pressure environmental scanning electronic microscope demonstrated that the amount of the ice crystals present in partially dried samples was lower than in the frozen samples. Holding the sperm at high subzero temperatures is necessary for the primary drying of cells during the freeze-drying process. Rapid freeze-drying can be achieved using this new device, which enables to reduce recrystallization damages.

  13. Gravimetric measurement of momentary drying rate of spray freeze-dried powders in vials.

    PubMed

    Gieseler, Henning; Lee, Geoffrey

    2009-09-01

    The profile of drying rate versus primary drying time for a spray freeze-dried trehalose aqueous solution is much different from that determined for regular freeze-drying. Drying rate declines very rapidly, attributed to rate-limiting heat transfer through the packed bed of frozen microparticles contained in a vial. The inter-particulate spaces appear to be the cause of this rate limitation. Use of either liquid nitrogen or liquid propane as a cryogenic produced strong differences in both SFD particle morphology and drying rate using trehalose, sucrose, or mannitol. The lack of any evident correlation supports the argument that the inter-particulate voids determine drying behavior.

  14. Physicochemical characterization of commercial freeze-dried snake antivenoms.

    PubMed

    Herrera, María; Solano, Daniela; Gómez, Aarón; Villalta, Mauren; Vargas, Mariángela; Sánchez, Andrés; Gutiérrez, José María; León, Guillermo

    2017-02-01

    Freeze-drying is a process used to improve the stability of pharmaceutical proteins, including snake antivenoms. This additional step confers these with a higher stability in comparison to liquid formulations, especially in tropical regions where high temperatures could affect the activity of immunoglobulins. Currently, the knowledge about freeze-drying process conditions for snake antivenoms is very limited. Some of the scarce scientific works on this subject reported reconstitution times up to 90 min for these preparations, which could imply a delay in the beginning of the antivenom therapy at the clinical setting. Therefore there is a reasonable concern about whether freeze-dried antivenoms exhibit the desired attributes for solid pharmaceutical proteins. In this work, a physicochemical characterization of seven commercial freeze-dried snake antivenoms was performed based on tests recommended by the World Health Organization (WHO). No significant differences were observed between the products regarding macroscopic appearance of the solid cakes, reconstitution times, residual humidity and monomers content. On the other hand, total protein concentration, turbidity and electrophoretic profile were different among samples. Microscopic analysis by scanning electron microscopy showed no collapsed structure and, instead, most of the samples showed a characteristic protein morphology composed of smooth plates and channels. All the parameters tested in this study were according to literature recommendations and evidenced that, in spite of slight variations found for some products, formulation and freeze-drying conditions chosen by manufacturers are adequate to prevent aggregation and generate, in physicochemical terms, freeze-dried antivenoms of acceptable quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Total phenolics content, anthocyanins, and dietary fiber content of apple pomace powders produced by vacuum-belt drying.

    PubMed

    Yan, Huitong; Kerr, William L

    2013-04-01

    Apple pomace is a waste material from apple juice processing, and contains significant amounts of dietary fiber and phytochemicals. Many of these compounds may be degraded post-pressing and during drying operations. Continuous vacuum-belt drying (VBD) was studied as a means of drying and maintaining quality of apple pomace. The color and chemical properties of samples dried by vacuum-belt drying at different temperatures were evaluated including total phenolics content (TPC), monomeric anthocyanins (TMA) and dietary fiber content (TDF). VBD powders were pale golden yellow, and those dried at 80°C did not differ in L*, a* and b* values from freeze-dried powders. VBD pomace had 44.9 to 51.9 g gallic acid equivalents kg(-1) TPC, with greatest retention for pomace dried at 80 and 95°C. TPC for pomace dried at 80 or 95°C was not significantly different from that for freeze-dried pomace. TMA levels (74.0 mg C3G kg(-1), where C3G is cyanidine 3-O-glucoside equivalents) were highest in pomace vacuum dried at 80°C. TDF ranged from 442 to 495 g kg(-1) in vacuum-dried pomace and was not significantly different from TDF of freeze-dried poamce (480 g kg(-1)). In all cases, TPC, TMA and TDF were higher in VBD pomace than in freeze-dried whole apple, while VBD pomace prepared at 80 or 95°C had fiber and phytochemical levels similar to freeze-dried powders. © 2012 Society of Chemical Industry.

  16. The effect of dryer load on freeze drying process design.

    PubMed

    Patel, Sajal M; Jameel, Feroz; Pikal, Michael J

    2010-10-01

    Freeze-drying using a partial load is a common occurrence during the early manufacturing stages when insufficient amounts of active pharmaceutical ingredient (API) are available. In such cases, the immediate production needs are met by performing lyophilization with less than a full freeze dryer load. However, it is not obvious at what fractional load significant deviations from full load behavior begin. The objective of this research was to systematically study the effects of variation in product load on freeze drying behavior in laboratory, pilot and clinical scale freeze-dryers. Experiments were conducted with 5% mannitol (high heat and mass flux) and 5% sucrose (low heat and mass flux) at different product loads (100%, 50%, 10%, and 2%). Product temperature was measured in edge as well as center vials with thermocouples. Specific surface area (SSA) was measured by BET gas adsorption analysis and residual moisture was measured by Karl Fischer. In the lab scale freeze-dryer, the molar flux of inert gas was determined by direct flow measurement using a flowmeter and the molar flux of water vapor was determined by manometric temperature measurement (MTM) and tunable diode laser absorption spectroscopy (TDLAS) techniques. Comparative pressure measurement (capacitance manometer vs. Pirani) was used to determine primary drying time. For both 5% mannitol and 5% sucrose, primary drying time decreases and product temperature increases as the load on the shelves decreases. No systematic variation was observed in residual moisture and vapor composition as load decreased. Further, SSA data suggests that there are no significant freezing differences under different load conditions. Independent of dryer scale, among all the effects, variation in radiation heat transfer from the chamber walls to the product seems to be the dominant effect resulting in shorter primary drying time as the load on the shelf decreases (i.e., the fraction of edge vials increases).

  17. Computational analysis of fluid dynamics in pharmaceutical freeze-drying.

    PubMed

    Alexeenko, Alina A; Ganguly, Arnab; Nail, Steven L

    2009-09-01

    Analysis of water vapor flows encountered in pharmaceutical freeze-drying systems, laboratory-scale and industrial, is presented based on the computational fluid dynamics (CFD) techniques. The flows under continuum gas conditions are analyzed using the solution of the Navier-Stokes equations whereas the rarefied flow solutions are obtained by the direct simulation Monte Carlo (DSMC) method for the Boltzmann equation. Examples of application of CFD techniques to laboratory-scale and industrial scale freeze-drying processes are discussed with an emphasis on the utility of CFD for improvement of design and experimental characterization of pharmaceutical freeze-drying hardware and processes. The current article presents a two-dimensional simulation of a laboratory scale dryer with an emphasis on the importance of drying conditions and hardware design on process control and a three-dimensional simulation of an industrial dryer containing a comparison of the obtained results with analytical viscous flow solutions. It was found that the presence of clean in place (CIP)/sterilize in place (SIP) piping in the duct lead to significant changes in the flow field characteristics. The simulation results for vapor flow rates in an industrial freeze-dryer have been compared to tunable diode laser absorption spectroscopy (TDLAS) and gravimetric measurements.

  18. Protein spheres prepared by drop jet freeze drying.

    PubMed

    Eggerstedt, Sören N; Dietzel, Mathias; Sommerfeld, Martin; Süverkrüp, Richard; Lamprecht, Alf

    2012-11-15

    In spray freeze drying (SFD) solutions are frozen by spraying into a very cold environment and subsequently dried by sublimation. In contrast to conventional freeze drying, spray freeze drying has the possibility to produce flowable lyophilizates which offers a variety of new pharmaceutical applications. Here, a drop jet nozzle is proposed as liquid dispenser that is able to produce droplets with a very narrow size distribution compared to standard methods. The drop jet nozzle is mounted in a spray tower designed to prevent direct contact of the product with the freezing medium. Various formulations have been tested containing lysozyme as model protein and stabilizers such as bovine serum albumin, polyvinylpyrrolidone or dextran in various concentrations and mannitol. Excellent free flowing and nearly monodispersed, porous particles are produced where particle properties can be controlled by formulation and process conditions. The particle diameter varied between 231 ± 3 μm and 310 ± 10 μm depending on the formulation composition. The lysozyme activity was >94 ± 5% for all formulations exhibiting a full preservation of enzyme activity. This new method is very promising for the production of nearly monodisperse particulate lyophilizates in various therapeutic applications. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Rehydration of freeze-dried and convective dried boletus edulis mushrooms: effect on some quality parameters.

    PubMed

    Hernando, I; Sanjuán, N; Pérez-Munuera, I; Mulet, A

    2008-10-01

    Quality of rehydrated products is a key aspect linked to rehydration conditions. To assess the effect of rehydration temperature on some quality parameters, experiments at 20 and 70 degrees C were performed with convective dried and freeze-dried Boletus edulis mushrooms. Rehydration characteristics (through Peleg's parameter, k(1), and equilibrium moisture, W(e)), texture (Kramer), and microstructure (Cryo-Scanning Electron Microscopy) were evaluated. Freeze-dried samples absorbed water more quickly and attained higher W(e) values than convective dried ones. Convective dehydrated samples rehydrated at 20 degrees C showed significantly lower textural values (11.9 +/- 3.3 N/g) than those rehydrated at 70 degrees C (15.7 +/- 1.2 N/g). For the freeze-dried Boletus edulis, the textural values also exhibited significant differences, being 8.2 +/- 1.3 and 10.5 +/- 2.3 N/g for 20 and 70 degrees C, respectively. Freeze-dried samples showed a porous structure that allows rehydration to take place mainly at the extracellular level. This explains the fact that, regardless of temperature, freeze-dried mushrooms absorbed water more quickly and reached higher W(e) values than convective dried ones. Whatever the dehydration technique used, rehydration at 70 degrees C produced a structural damage that hindered water absorption; consequently lower W(e) values and higher textural values were attained than when rehydrating at 20 degrees C.

  20. A model for the effect of real leaks on the transport of microorganisms into a vacuum freeze-dryer.

    PubMed

    Jennings, T A

    1990-01-01

    This paper proposes a model for determining the effect that real leaks, whose flow is viscous in nature, could have on the microorganism density in a vacuum freeze-dryer during a drying process. The model considers the entry of microorganisms to result from real leaks stemming from an environment containing a known bioburden. A means for determining the relationship between the rate of pressure rise of the system (ROR) and the density of microorganisms in a system, stemming from an environment of a known bioburden, is examined. The model also considers the change in the bioburden of the dryer with respect to variations in the primary and secondary drying process.

  1. Correlation of laboratory and production freeze drying cycles.

    PubMed

    Kuu, Wei Y; Hardwick, Lisa M; Akers, Michael J

    2005-09-30

    The purpose of this study was to develop the correlation of cycle parameters between a laboratory and a production freeze-dryer. With the established correlation, key cycle parameters obtained using a laboratory dryer may be converted to those for a production dryer with minimal experimental efforts. In order to develop the correlation, it was important to consider the contributions from the following freeze-drying components: (1) the dryer, (2) the vial, and (3) the formulation. The critical parameters for the dryer are the shelf heat transfer coefficient and shelf surface radiation emissivity. The critical parameters for the vial are the vial bottom heat transfer coefficients (the contact parameter Kcs and separation distance lv), and vial top heat transfer coefficient. The critical parameter of the formulation is the dry layer mass transfer coefficient. The above heat and mass transfer coefficients were determined by freeze-drying experiments in conjunction with mathematical modeling. With the obtained heat and mass transfer coefficients, the maximum product temperature, Tbmax, during primary drying was simulated using a primary drying subroutine as a function of the shelf temperature and chamber pressure. The required shelf temperature and chamber pressure, in order to perform a successful cycle run without product collapse, were then simulated based on the resulting values of Tbmax. The established correlation approach was demonstrated by the primary drying of the model formulation 5% mannitol solution. The cycle runs were performed using a LyoStar dryer as the laboratory dryer and a BOC Edwards dryer as the production dryer. The determined normalized dried layer mass transfer resistance for 5% mannitol is expressed as RpN=0.7313+17.19l, where l is the receding dry layer thickness. After demonstrating the correlation approach using the model formulation 5% mannitol, a practical comparison study was performed for the actual product, the lactate dehydrogenase

  2. Effects of ultrasonic pretreatments on quality, energy consumption and sterilization of barley grass in freeze drying.

    PubMed

    Cao, Xiaohuang; Zhang, Min; Mujumdar, Arun S; Zhong, Qifeng; Wang, Zhushang

    2018-01-01

    Barley grass is a plant resource for rehabilitation therapy. Its processing requires retaining nutrition well for rehabilitation cure of consumers. To meet the aim as well as low energy consumption and microbiological safety of products, ultrasonic treatments (UT) were applied to bathing materials at different power levels (10, 30, 45, 60W/L) for 10mins. After treatments, the bathed barley grass (100g) was freeze-dried under vacuum -0.09MPa with fixed power of 2W/g. Parameters of color, microbial colony, energy consumption, glass transition temperature, moisture content, water activity, taste substances, contents of flavonoid and chlorophyll were determined after drying. In contrast with no treatment case, UT (45W/L) decreased drying time by 14% and decreased energy consumption by 19%; UT (60W/L) decreased total microbial colonies by 33%. Also, UT (30W/L) yielded contents of flavonoid (9.2/kg) and chlorophyll (10.5g/kg) of dried sample; UT power (10W/L) yielded the highest L ∗ (51.5) and the lowest a ∗ (-9.3) value. Simultaneously, UT leads to a higher glass transition temperature (Tg), lower water activity and produces less sourness and bitterness of dried products. Ultra-sonication is an alternative to improve quality, flavor and energy consumption of barley grass in freeze drying. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Particulate contamination from siliconized rubber closures for freeze drying.

    PubMed

    Gebhardt, U; Grumbridge, N A; Knoch, A

    1996-01-01

    It can be shown that siliconized closures for freeze drying may cause the opalescence and turbidity observed in freeze-dried products after reconstitution. Closures of different rubber composition show different intensities of turbidity when treated identically with the same quantity and type of silicone oil. Clear solutions are obtained after reconstitution if ETFE-coated closures are used instead of siliconized closures. Samples stored at 4 degrees C for up to 6 months show no change in the intensity of turbidity, while the turbidity of samples manufactured with siliconized closures and stored at higher temperatures increase with time. Samples with ETFE-coated closures show clear solutions when stored at 25 degrees C and 37 degrees C for up to 6 months and at 45 degrees C for 3 months. After 6 months only a very weak opalescence could be observed in these samples.

  4. Heat and Mass Transfer Model in Freeze-Dried Medium

    NASA Astrophysics Data System (ADS)

    Alfat, Sayahdin; Purqon, Acep

    2017-07-01

    There are big problems in agriculture sector every year. One of the major problems is abundance of agricultural product during the peak of harvest season that is not matched by an increase in demand of agricultural product by consumers, this causes a wasted agricultural products. Alternative way was food preservation by freeze dried method. This method was already using heat transfer through conduction and convection to reduce water quality in the food. The main objective of this research was to design a model heat and mass transfer in freeze-dried medium. We had two steps in this research, the first step was design of medium as the heat injection site and the second was simulate heat and mass transfer of the product. During simulation process, we use physical property of some agriculture product. The result will show how temperature and moisture distribution every second. The method of research use finite element method (FEM) and will be illustrated in three dimensional.

  5. Shrinkage of spray-freeze-dried microparticles of pure protein for ballistic injection by manipulation of freeze-drying cycle.

    PubMed

    Straller, Georg; Lee, Geoffrey

    2017-10-30

    Spray-freeze-drying was used to produce shrivelled, partially-collapsed microparticles of pure proteins that may be suitable for use in a ballistic injector. Various modifications of the freeze drying cycle were examined for their effects on collapse of the pure protein microparticles. The use of annealing at a shelf temperature of up to +10°C resulted in no visible particle shrinkage. This was because of the high T g ' of the pure protein. Inclusion of trehalose or sucrose led to particle shrinkage because of the plasticizing effects of the disaccharides on the protein. Only by extending the duration of primary drying from 240 to 2745min at shelf temperatures in the range -12 to -8°C were shrivelled, wrinkled particles of bSA and bCA of reduced porosity obtained. Manipulation of the freeze-drying cycle used for SFD can therefore be used to modify particle morphology and increase particle density. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Cancer prevention with freeze-dried berries and berry components.

    PubMed

    Stoner, Gary D; Wang, Li-Shu; Zikri, Nancy; Chen, Tong; Hecht, Stephen S; Huang, Chuanshu; Sardo, Christine; Lechner, John F

    2007-10-01

    Our laboratory is developing a food-based approach to the prevention of esophageal and colon cancer utilizing freeze-dried berries and berry extracts. Dietary freeze-dried berries were shown to inhibit chemically induced cancer of the rodent esophagus by 30-60% and of the colon by up to 80%. The berries are effective at both the initiation and promotion/progression stages of tumor development. Berries inhibit tumor initiation events by influencing carcinogen metabolism, resulting in reduced levels of carcinogen-induced DNA damage. They inhibit promotion/progression events by reducing the growth rate of pre-malignant cells, promoting apoptosis, reducing parameters of tissue inflammation and inhibiting angiogenesis. On a molecular level, berries modulate the expression of genes involved with proliferation, apoptosis, inflammation and angiogenesis. We have recently initiated clinical trials; results from a toxicity study indicated that freeze-dried black raspberries are well tolerated in humans when administered orally for 7 days at a dose of 45 g per day. Several Phase IIa clinical trials are underway in patients at high risk for esophagus and colon cancer; i.e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases.

  7. Cancer Prevention with Freeze-dried Berries and Berry Components

    PubMed Central

    Stoner, Gary D.; Wang, Li-Shu; Zikri, Nancy; Chen, Tong; S. Hecht, Stephen; Huang, Chuanshu; Sardo, Christine; Lechner, John F.

    2007-01-01

    Our laboratory is developing a food-based approach to the prevention of esophageal and colon cancer utilizing freeze-dried berries and berry extracts. Dietary freeze-dried berries were shown to inhibit chemically-induced cancer of the rodent esophagus by 30-60% and of the colon by up- to 80%. The berries are effective at both the initiation and promotion/progression stages of tumor development. Berries inhibit tumor initiation events by influencing carcinogen metabolism, resulting in reduced levels of carcinogen-induced DNA damage. They inhibit promotion/progression events by reducing the growth rate of premalignant cells, promoting apoptosis, reducing parameters of tissue inflammation and inhibiting angiogenesis. On a molecular level, berries modulate the expression of genes involved with proliferation, apoptosis, inflammation and angiogenesis. We have recently initiated clinical trials; results from a toxicity study indicated that freeze-dried black raspberries are well tolerated in humans when administered orally for 7 days at a dose of 45 grams per day. Several Phase IIa clinical trials are underway in patients at high risk for esophagus and colon cancer; i.e., Barrett’s esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases. PMID:17574861

  8. Moisture sorption characteristics of freeze-dried human platelets*

    PubMed Central

    Xu, Meng-jie; Chen, Guang-ming; Fan, Ju-li; Liu, Jin-hui; Xu, Xian-guo; Zhang, Shao-zhi

    2011-01-01

    Freeze-drying is a promising method for a long-term storage of human platelets. The moisture sorption characteristics of freeze-dried human platelets (FDHPs) were studied in this paper. The moisture sorption isotherms of FDHPs and freeze-dried lyophilization buffer (FDLB) were measured at 4, 25, and 37 °C. The experimental data were fitted to Brunauer-Emmett-Teller (BET) and Guggenheim-Anderson-de Boer (GAB) equations. There were no significant statistical differences (P>0.05) between the sorption characteristics of FDHPs and FDLB at 4 and 25 °C, while FDHPs absorbed more water at 37 °C. The net isosteric heat of sorption was derived. The heat for FDHPs showed an abnormal negative value at low moisture contents when 25 and 37 °C data were used. Dynamic sorption experiments were carried out at 25 °C with environmental water activity controlled at 0.75, 0.85, and 0.90. The moisture diffusion coefficient was fitted to be 8.24×10−12 m2/s when experimental data at initial time were used. These results would be helpful in choosing prehydration and storage condition for FDHPs. PMID:21370506

  9. Optimization of protectant, salinity and freezing condition for freeze-drying preservation of Edwardsiella tarda

    NASA Astrophysics Data System (ADS)

    Yu, Yongxiang; Zhang, Zheng; Wang, Yingeng; Liao, Meijie; Li, Bin; Xue, Liangyi

    2017-10-01

    Novel preservation condition without ultra-low temperature is needed for the study of pathogen in marine fishes. Freeze-drying is such a method usually used for preservation of terrigenous bacteria. However, studies using freeze-drying method to preserving marine microorganisms remain very limited. In this study, we optimized the composition of protectants during the freeze-drying of Edwardsiella tarda, a fish pathogen that causes systemic infection in marine fishes. We found that the optimal composition of protectant mixture contained trehalose (8.0%), skim milk (12.0%), sodium citrate (2.0%), serum (12.0%) and PVP (2.0%). Orthogonal and interaction analyses demonstrated the interaction between serum and skim milk or sodium citrate. The highest survival rate of E. tarda was observed when the concentration of NaCl was 10.0, 30.0 and between 5.0 and 10.0 g L-1 for preparing TSB medium, E. tarda suspension and protectant mixture, respectively. When E. tarda was frozen at -80°C or -40°C for 6 h, its survival rate was higher than that under other tested conditions. Under the optimized conditions, when the protectant mixture was used during freeze-drying process, the survival rate (79.63%-82.30%) of E. tarda was significantly higher than that obtained using single protectant. Scanning electron microscopy (SEM) image indicated that E. tarda was embedded in thick matrix with detectable aggregation. In sum, the protectant mixture may be used as a novel cryoprotective additive for E. tarda.

  10. Accurate prediction of collapse temperature using optical coherence tomography-based freeze-drying microscopy.

    PubMed

    Greco, Kristyn; Mujat, Mircea; Galbally-Kinney, Kristin L; Hammer, Daniel X; Ferguson, R Daniel; Iftimia, Nicusor; Mulhall, Phillip; Sharma, Puneet; Kessler, William J; Pikal, Michael J

    2013-06-01

    The objective of this study was to assess the feasibility of developing and applying a laboratory tool that can provide three-dimensional product structural information during freeze-drying and which can accurately characterize the collapse temperature (Tc ) of pharmaceutical formulations designed for freeze-drying. A single-vial freeze dryer coupled with optical coherence tomography freeze-drying microscopy (OCT-FDM) was developed to investigate the structure and Tc of formulations in pharmaceutically relevant products containers (i.e., freeze-drying in vials). OCT-FDM was used to measure the Tc and eutectic melt of three formulations in freeze-drying vials. The Tc as measured by OCT-FDM was found to be predictive of freeze-drying with a batch of vials in a conventional laboratory freeze dryer. The freeze-drying cycles developed using OCT-FDM data, as compared with traditional light transmission freeze-drying microscopy (LT-FDM), resulted in a significant reduction in primary drying time, which could result in a substantial reduction of manufacturing costs while maintaining product quality. OCT-FDM provides quantitative data to justify freeze-drying at temperatures higher than the Tc measured by LT-FDM and provides a reliable upper limit to setting a product temperature in primary drying. Copyright © 2013 Wiley Periodicals, Inc.

  11. Cold Vacuum Drying (CVD) Facility Acceptance for Beneficial Use

    SciT

    BRISBIN, S.A.

    2000-01-05

    This document provides a checklist of the items required for turnover of the Cold Vacuum Drying Facility from the Construction Projects organization to the Operations organization. This document will be updated periodically to document completion of additional deliverables.

  12. Calorimetric analysis of cryopreservation and freeze-drying formulations.

    PubMed

    Sun, Wendell Q

    2015-01-01

    Differential scanning calorimetry (DSC) is a commonly used thermal analysis technique in cryopreservation and freeze-drying research. It has been used to investigate crystallization, eutectic formation, glass transition, devitrification, recrystallization, melting, polymorphism, molecular relaxation, phase separation, water transport, thermochemistry, and kinetics of complex reactions (e.g., protein denaturation). Such information can be used for the optimization of protective formulations and process protocols. This chapter gives an introduction to beginners who are less familiar with this technique. It covers the instrument and its basic principles, followed by a discussion of the methods as well as examples of specific applications.

  13. Determination of end point of primary drying in freeze-drying process control.

    PubMed

    Patel, Sajal M; Doen, Takayuki; Pikal, Michael J

    2010-03-01

    Freeze-drying is a relatively expensive process requiring long processing time, and hence one of the key objectives during freeze-drying process development is to minimize the primary drying time, which is the longest of the three steps in freeze-drying. However, increasing the shelf temperature into secondary drying before all of the ice is removed from the product will likely cause collapse or eutectic melt. Thus, from product quality as well as process economics standpoint, it is very critical to detect the end of primary drying. Experiments were conducted with 5% mannitol and 5% sucrose as model systems. The apparent end point of primary drying was determined by comparative pressure measurement (i.e., Pirani vs. MKS Baratron), dew point, Lyotrack (gas plasma spectroscopy), water concentration from tunable diode laser absorption spectroscopy, condenser pressure, pressure rise test (manometric temperature measurement or variations of this method), and product thermocouples. Vials were pulled out from the drying chamber using a sample thief during late primary and early secondary drying to determine percent residual moisture either gravimetrically or by Karl Fischer, and the cake structure was determined visually for melt-back, collapse, and retention of cake structure at the apparent end point of primary drying (i.e., onset, midpoint, and offset). By far, the Pirani is the best choice of the methods tested for evaluation of the end point of primary drying. Also, it is a batch technique, which is cheap, steam sterilizable, and easy to install without requiring any modification to the existing dryer.

  14. Application of the Quality by Design Approach to the Freezing Step of Freeze-Drying: Building the Design Space.

    PubMed

    Arsiccio, Andrea; Pisano, Roberto

    2018-06-01

    The present work shows a rational method for the development of the freezing step of a freeze-drying cycle. The current approach to the selection of freezing conditions is still empirical and nonsystematic, thus resulting in poor robustness of control strategy. The final aim of this work is to fill this gap, describing a rational procedure, based on mathematical modeling, for properly choosing the freezing conditions. Mechanistic models are used for the prediction of temperature profiles during freezing and dimension of ice crystals being formed. Mathematical description of the drying phase of freeze-drying is also coupled with the results obtained by freezing models, thus providing a comprehensive characterization of the lyophilization process. In this framework, deep understanding of the phenomena involved is required, and according to the Quality by Design approach, this knowledge can be used to build the design space. The step-by-step procedure for building the design space for freezing is thus described, and examples of applications are provided. The calculated design space is validated upon experimental data, and we show that it allows easy control of the freezing process and fast selection of appropriate operating conditions. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Survival differences among freeze-dried genetically engineered and wild-type bacteria.

    PubMed Central

    Israeli, E; Shaffer, B T; Hoyt, J A; Lighthart, B; Ganio, L M

    1993-01-01

    Because the death mechanisms of freeze-dried and air-dried bacteria are thought to be similar, freeze-drying was used to investigate the survival differences between potentially airborne genetically engineered microorganisms and their wild types. To this end, engineered strains of Escherichia coli and Pseudomonas syringae were freeze-dried and exposed to air, visible light, or both. The death rates of all engineered strains were significantly higher than those of their parental strains. Light and air exposure were found to increase the death rates of all strains. Application of death rate models to freeze-dried engineered bacteria to be released into the environment is discussed. PMID:8434925

  16. Modelling of nectarine drying under near infrared - Vacuum conditions.

    PubMed

    Alaei, Behnam; Chayjan, Reza Amiri

    2015-01-01

    Drying of nectarine slices was performed to determine the thermal and physical properties in order to reduce product deterioration due to chemical reactions, facilitate storage and lower transportation costs. Because nectarine slices are sensitive to heat with long drying period, the selection of a suitable drying approach is a challenging task. Infrared-vacuum drying can be used as an appropriate method for susceptible materials with high moisture content such as nectarine slices. Modelling of nectarine slices drying was carried out in a thin layer near infraredvacuum conditions. Drying of the samples was implemented at the absolute pressures of 20, 40 and 60 kPa and drying temperatures of 50, 60 and 70°C. Drying behaviour of nectarine slices, as well as the effect of drying conditions on moisture loss trend, drying rate, effective diffusion coefficient, activation energy, shrinkage, colour and energy consumption of nectarine slices, dried in near infrared-vacuum dryer are discussed in this study. Six mathematical models were used to predict the moisture ratio of the samples in thin layer drying. The Midilli model had supremacy in prediction of nectarine slices drying behaviour. The maximum drying rates of the samples were between 0.014-0.047 gwater/gdry material·min. Effective moisture diffusivity of the samples was estimated in the ranges of 2.46·10-10 to 6.48·10-10 m2/s. Activation energy were computed between 31.28 and 35.23 kJ/mol. Minimum shrinkage (48.4%) and total colour difference (15.1) were achieved at temperature of 50°C and absolute pressure of 20 kPa. Energy consumption of the tests was estimated in the ranges of 0.129 to 0.247 kWh. Effective moisture diffusivity was increased with decrease of vacuum pressure and increase of drying temperature but effect of drying temperature on effective moisture diffusivity of nectarine slices was more than vacuum pressure. Activation energy was decreased with decrease in absolute pressure. Total colour

  17. Application of freeze-drying technology in manufacturing orally disintegrating films.

    PubMed

    Liew, Kai Bin; Odeniyi, Michael Ayodele; Peh, Kok-Khiang

    2016-01-01

    Freeze drying technology has not been maximized and reported in manufacturing orally disintegrating films. The aim of this study was to explore the freeze drying technology in the formulation of sildenafil orally disintegrating films and compare the physical properties with heat-dried orally disintegrating film. Central composite design was used to investigate the effects of three factors, namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the tensile strength and disintegration time of the film. Heat-dried films had higher tensile strength than films prepared using freeze-dried method. For folding endurance, freeze-dried films showed improved endurance than heat-dried films. Moreover, films prepared using freeze-dried methods were thicker and had faster disintegration time. Formulations with higher amount of carbopol and starch showed higher tensile strength and thickness whereas formulations with higher PEG 400 content showed better flexibility. Scanning electron microscopy showed that the freeze-dried films had more porous structure compared to the heat-dried film as a result of the release of water molecule from the frozen structure when it was subjected to freeze drying process. The sildenafil film was palatable. The dissolution profiles of freeze-dried and heat-dried films were similar to Viagra® with f2 of 51.04 and 65.98, respectively.

  18. Cold Vacuum Drying (CVD) Set Point Determination

    SciT

    PHILIPP, B.L.

    2000-03-21

    The Safety Class Instrumentation and Control (SCIC) system provides active detection and response to process anomalies that, if unmitigated, would result in a safety event. Specifically, actuation of the SCIC system includes two portions. The portion which isolates the MCO and initiates the safety-class helium (SCHe) purge, and the portion which detects and stops excessive heat input to the MCO on high tempered water MCO inlet temperature. For the MCO isolation and purge, the SCIC receives signals from MCO pressure (both positive pressure and vacuum), helium flow rate, bay high temperature switches, seismic trips and time under vacuum trips.

  19. Optimization of the secondary drying step in freeze drying using TDLAS technology.

    PubMed

    Schneid, Stefan C; Gieseler, Henning; Kessler, William J; Luthra, Suman A; Pikal, Michael J

    2011-03-01

    The secondary drying phase in freeze drying is mostly developed on a trial-and-error basis due to the lack of appropriate noninvasive process analyzers. This study describes for the first time the application of Tunable Diode Laser Absorption Spectroscopy, a spectroscopic and noninvasive sensor for monitoring secondary drying in laboratory-scale freeze drying with the overall purpose of targeting intermediate moisture contents in the product. Bovine serum albumin/sucrose mixtures were used as a model system to imitate high concentrated antibody formulations. First, the rate of water desorption during secondary drying at constant product temperatures (-22 °C, -10 °C, and 0 °C) was investigated for three different shelf temperatures. Residual moisture contents of sampled vials were determined by Karl Fischer titration. An equilibration step was implemented to ensure homogeneous distribution of moisture (within 1%) in all vials. The residual moisture revealed a linear relationship to the water desorption rate for different temperatures, allowing the evaluation of an anchor point from noninvasive flow rate measurements without removal of samples from the freeze dryer. The accuracy of mass flow integration from this anchor point was found to be about 0.5%. In a second step, the concept was successfully tested in a confirmation experiment. Here, good agreement was found for the initial moisture content (anchor point) and the subsequent monitoring and targeting of intermediate moisture contents. The present approach for monitoring secondary drying indicated great potential to find wider application in sterile operations on production scale in pharmaceutical freeze drying. © 2011 American Association of Pharmaceutical Scientists

  20. Effect of drying methods with the application of vacuum microwaves on the bioactive compounds, color, and antioxidant activity of strawberry fruits.

    PubMed

    Wojdyło, Aneta; Figiel, Adam; Oszmiański, Jan

    2009-02-25

    The objective of this study was to evaluate the application of vacuum-microwave drying (240, 360, and 480 W) in the production process of dehydrated strawberry and to compare and contrast the quality of these dehydrated strawberries in terms of their polyphenol compounds, concentration of some heat liable components, and color to that of freeze-dried, convective, and vacuum-dried strawberry. Thus, the effect of vacuum-microwave drying and other drying methods on the antioxidant activity of berries was evaluated. Whole fresh and dried fruits were assessed for phenolics (anthocyanins, flavanols, hydroxycinnamic acids, and flavonols), ascorbic acid, and antioxidant activity (all parameters were calculated on a dry matter basis). Analysis of data shows that ellagic acid and flavanol changes were affected by drying techniques and cultivar. Drying destroyed anthocyanins, flavanols, and ascorbic acid, and there was a significant decrease in antioxidant activity. The most striking result was that conventional and vacuum drying decreased antioxidant activity in both cultivars, whereas contradictory results were found for vacuum-microwave processed strawberry. This study has demonstrated that vacuum-microwave drying, especially at 240 W, can produce high-quality products, with the additional advantage of reduced processing times, compared to other processes such as freeze-drying.

  1. Optical extinction of highly porous aerosol following atmospheric freeze drying

    NASA Astrophysics Data System (ADS)

    Adler, Gabriela; Haspel, Carynelisa; Moise, Tamar; Rudich, Yinon

    2014-06-01

    Porous glassy particles are a potentially significant but unexplored component of atmospheric aerosol that can form by aerosol processing through the ice phase of high convective clouds. The optical properties of porous glassy aerosols formed from a freeze-dry cycle simulating freezing and sublimation of ice particles were measured using a cavity ring down aerosol spectrometer (CRD-AS) at 532 nm and 355 nm wavelength. The measured extinction efficiency was significantly reduced for porous organic and mixed organic-ammonium sulfate particles as compared to the extinction efficiency of the homogeneous aerosol of the same composition prior to the freeze-drying process. A number of theoretical approaches for modeling the optical extinction of porous aerosols were explored. These include effective medium approximations, extended effective medium approximations, multilayer concentric sphere models, Rayleigh-Debye-Gans theory, and the discrete dipole approximation. Though such approaches are commonly used to describe porous particles in astrophysical and atmospheric contexts, in the current study, these approaches predicted an even lower extinction than the measured one. Rather, the best representation of the measured extinction was obtained with an effective refractive index retrieved from a fit to Mie scattering theory assuming spherical particles with a fixed void content. The single-scattering albedo of the porous glassy aerosols was derived using this effective refractive index and was found to be lower than that of the corresponding homogeneous aerosol, indicating stronger relative absorption at the wavelengths measured. The reduced extinction and increased absorption may be of significance in assessing direct, indirect, and semidirect forcing in regions where porous aerosols are expected to be prevalent.

  2. Microwave-Osmotic/Microwave-Vacuum Drying of Whole Cranberries: Comparison with Other Methods.

    PubMed

    Wray, Derek; Ramaswamy, Hosahalli S

    2015-12-01

    A novel drying method for frozen-thawed whole cranberries was developed by combining microwave osmotic dehydration under continuous flow medium spray (MWODS) conditions with microwave vacuum finish-drying. A central composite rotatable design was used to vary temperature (33 to 67 °C), osmotic solution concentration (33 to 67 °B), contact time (5 to 55 min), and flow rate (2.1 to 4.1 L/min) in order to the determine the effects of MWODS input parameters on quality of the dried berry. Quality indices monitored included colorimetric and textural data in addition to anthocyanin retention and cellular structure. Overall it was found that the MWODS-MWV process was able to produce dried cranberries with quality comparable to freeze dried samples in much shorter time. Additionally, cranberries dried via the novel process exhibited much higher quality than those dried via either vacuum or convective air drying in terms of color, anthocyanin content, and cellular structure. © 2015 Institute of Food Technologists®

  3. Inspection qualification (IQ) and operational qualification (OQ) for a vacuum freeze-dryer--Part I. General discussion.

    PubMed

    Jennings, T A; Scheer, A; Emodi, A; Puderbach, L; King, S; Norton, T

    1996-01-01

    The principle objectives of this paper are (a), to develop the rationale for conducting an inspection qualification (IQ) and operational qualification (OQ) of a vacuum freeze-dryer; (b), to identify the key elements that require verification for completion of the IQ; and (c), to establish the necessary environmental and operational parameters necessary for the OQ of the vacuum freeze-dryer.

  4. Folic acid content in thermostabilized and freeze-dried space shuttle foods

    NASA Technical Reports Server (NTRS)

    Lane, H. W.; Nillen, J. L.; Kloeris, V. L.

    1995-01-01

    This study was designed to determine whether freeze-dried and thermostabilized foods on a space shuttle contain adequate folate and to investigate any effects of freeze-drying on folacin. Frozen vegetables were analyzed after three states of processing: thawed; cooked; and rehydrated. Thermostabilized items were analyzed as supplied with no further processing. Measurable folate decreased in some freeze-dried vegetables and increased in others. Folacin content of thermostabilized food items was comparable with published values. We concluded that although the folacin content of some freeze-dried foods was low, adequate folate is available from the shuttle menu to meet RDA guidelines.

  5. Spent nuclear fuel project cold vacuum drying facility operations manual

    SciT

    IRWIN, J.J.

    This document provides the Operations Manual for the Cold Vacuum Drying Facility (CVDF). The Manual was developed in conjunction with HNF-SD-SNF-SAR-002, Safety Analysis Report for the Cold Vacuum Drying Facility, Phase 2, Supporting Installation of Processing Systems (Garvin 1998) and, the HNF-SD-SNF-DRD-002, 1997, Cold Vacuum Drying Facility Design Requirements, Rev. 3a. The Operations Manual contains general descriptions of all the process, safety and facility systems in the CVDF, a general CVD operations sequence, and has been developed for the SNFP Operations Organization and shall be updated, expanded, and revised in accordance with future design, construction and startup phases of themore » CVDF until the CVDF final ORR is approved.« less

  6. Freeze-drying in novel container system: Characterization of heat and mass transfer in glass syringes.

    PubMed

    Patel, Sajal M; Pikal, Michael J

    2010-07-01

    This study is aimed at characterizing and understanding different modes of heat and mass transfer in glass syringes to develop a robust freeze-drying process. Two different holder systems were used to freeze-dry in syringes: an aluminum (Al) block and a plexiglass holder. The syringe heat transfer coefficient was characterized by a sublimation test using pure water. Mannitol and sucrose (5% w/v) were also freeze-dried, as model systems, in both the assemblies. Dry layer resistance was determined from manometric temperature measurement (MTM) and product temperature was measured using thermocouples, and was also determined from MTM. Further, freeze-drying process was also designed using Smart freeze-dryer to assess its application for freeze-drying in novel container systems. Heat and mass transfer in syringes were compared against the traditional container system (i.e., glass tubing vial). In the Al block, the heat transfer was via three modes: contact conduction, gas conduction, and radiation with gas conduction being the dominant mode of heat transfer. In the plexiglass holder, the heat transfer was mostly via radiation; convection was not involved. Also, MTM/Smart freeze-drying did work reasonably well for freeze-drying in syringes. When compared to tubing vials, product temperature decreases and hence drying time increases in syringes. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  7. [Preparation of freeze-dried powder of recombinate hirudin-2 nanoparticle for nasal delivery and permeability through nasal membrane in vitro].

    PubMed

    Chen, Ming-Xia; Zhang, Jian-Bao; Yu, Ji-Ping; Ye, Jing; Wei, Bao-Hong; Zhang, Yu-Jie

    2013-06-01

    To optimize the freeze-dried powder preparation technology of recombinate hirudin-2 (rHV2) nanoparticle which has bio-adhesive characteristic for nasal delivery, also to investigate its stability and permeability through nasal membrane in vitro. Taking the appearance, rediffusion of nanoparticle and rHV2 encapsulation efficiency as the evaluation indexes. Cryoprotector, the preparative technique and the effect of illumination and high temperature factors on its stability for rHV2 freeze-dried powder were investigated. Using Fraze diffusion cell technique, the permeability of rHV2 across rabbit nasal mucous membrane in chitosan solution, chitosan nanoparticle, and nanoparticle frozen-dried powder were compared with that in normal saline solution. The optimized preparation of rHV2 nanoparticle freeze-dried powder was as follows: 5% trehalose and glucose (1:1) was used as cryoprotector, nanoparticle solution was freezed for 24 h in vacuum frozen-dryer after being pre-freezed for 24 h. The content of rHV2 in the freeze-dried powder was 1.1 ug/mg. Illumination had little effect on the appearance, rediffusion and encapsulation efficiency of the rHV2 freeze-dried powder. High temperature could obviously influence the appearance of nanoparticle freeze-dried powder. The permeability coefficient (P) of nanoparticle was 5 times more than that in chictonson solution. It was indicated that chitosan nanoparticle has effect on increasing the permeability of rHV2. The freeze-dried powder of chitosan nanoparticle can be a good nasal preparation of rHV2.

  8. Freeze drying vs microwave drying-methods for synthesis of sinteractive thoria powders

    NASA Astrophysics Data System (ADS)

    Annie, D.; Chandramouli, V.; Anthonysamy, S.; Ghosh, Chanchal; Divakar, R.

    2017-02-01

    Thoria powders were synthesized by oxalate precipitation from an aqueous solution of the nitrate. The filtered precipitates were freeze dried or microwave dried before being calcined at 1073 K. The thoria powders obtained were characterized for crystallite size, specific surface area, bulk density, particle size distribution and residual carbon. Microstructure of the product was studied using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Sinterability of the synthesized powders was studied by measuring the density of the sintered compacts. Powders that can be consolidated and sintered to densities ∼96% theoretical density (TD) at 1773 K were obtained.

  9. Simulation of the process kinetics and analysis of physicochemical properties in the freeze drying of kale

    NASA Astrophysics Data System (ADS)

    Dziki, Dariusz; Polak, Renata; Rudy, Stanisław; Krzykowski, Andrzej; Gawlik-Dziki, Urszula; Różyło, Renata; Miś, Antoni; Combrzyński, Maciej

    2018-01-01

    Investigations were performed to study the freeze-drying process of kale (Brassica oleracea L. var acephala). The process of freeze-drying was performed at temperatures of 20, 40, and 60°C for whole pieces of leaves and for pulped leaves. The kinetics of the freeze-drying of both kale leaves and kale pulp were best described by the Page model. The increasing freeze-drying temperature from 20 to 60°C induced an approximately two-fold decrease in the drying time. Freeze-drying significantly increased the value of the lightness, delta Chroma, and browning index of kale, and had little influence on the hue angle. The highest increase in the lightness and delta Chroma was observed for whole leaves freeze-dried at 20°C. An increase in the drying temperature brought about a slight decrease in the lightness, delta Chroma and the total colour difference. Pulping decreased the lightness and hue angle, and increased browning index. Freeze-drying engendered a slight decrease in the total phenolics content and antioxidant activity, in comparison to fresh leaves. The temperature of the process and pulping had little influence on the total phenolics content and antioxidant activity of dried kale, but significantly decreased the contents of chlorophyll a and chlorophyll b.

  10. A freeze-dried injectable form of ibuprofen: development and optimisation using response surface methodology.

    PubMed

    Kagkadis, K A; Rekkas, D M; Dallas, P P; Choulis, N H

    1996-01-01

    In this study a complex of Ibuprofen and b-Hydroxypropylcyclodextrin was prepared employing a freeze drying method. The production parameters and the final specifications of this product were optimized by using response surface methodology. The results show that the freeze dried complex meets the requirements for solubility to be considered as a possible injectable form.

  11. Development of a Method to Produce Freeze-Dried Cubes from 3 Pacific Salmon Species

    Freeze-dried boneless skinless cubes of pink (Oncorhynchus gorbuscha), sockeye (Oncorhynchus nerka), and chum (Oncorhynchus keta) salmon were prepared and physical properties evaluated. To minimize freeze-drying time, the kinetics of dehydration and processing yields were investigated. The physical ...

  12. Effect of moisture content on the invertase activity of freeze-dried S. cerevisiae.

    PubMed

    Pitombo, R N; Spring, C; Passos, R F; Tonato, M; Vitolo, M

    1994-08-01

    The invertase activity of intact Saccharomyces cerevisiae submitted to freezing-thawing was affected by pH, the chemical nature of the buffer, and the freezing cooling rate (CR), leading in some cases to a complete invertase inactivation (acetate buffer, pH 4.0, CR = 0.5 degree C/min). Once established under adequate freezing conditions the invertase activity remained unchanged after freeze-drying. Nevertheless, in some cases the cell-growing capability after freeze-drying diminished around 70%, mainly if the frozen cell suspension was attained through freezing carried out at CR = 0.5 degree C/min. Water sorption isotherms of freeze-dried samples (freeze-dryer Edwards L-4KR; 30 degrees C and 0.1 mB) were determined at 10 and 25 degrees C. The monolayer moisture content (MMC) at each temperature (12.7 and 3.71 for 10 and 25 degrees C, respectively) was calculated from isotherms by applying BET and GAB models. Freeze-dried yeast with water activity (Aw) between 0 and 0.33 (about the MMC value) maintained at 25 degrees C for 235 days and at 89 degrees C for 15 min retained at least 85% of its original invertase activity (IA), whereas samples with Aw > MMC lost at least 60% of its IA. X ray diffraction showed that the freeze-dried cake before and after storage presented an amorphous structure.

  13. Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying

    PubMed Central

    Okuda, Tomoyuki; Suzuki, Yumiko; Kobayashi, Yuko; Ishii, Takehiko; Uchida, Satoshi; Itaka, Keiji; Kataoka, Kazunori; Okamoto, Hirokazu

    2015-01-01

    In this study, two types of biodegradable polycation (PAsp(DET) homopolymer and PEG-PAsp(DET) copolymer) were applied as vectors for inhalable dry gene powders prepared by spray freeze drying (SFD). The prepared dry gene powders had spherical and porous structures with a 5~10-μm diameter, and the integrity of plasmid DNA could be maintained during powder production. Furthermore, it was clarified that PEG-PAsp(DET)-based dry gene powder could more sufficiently maintain both the physicochemical properties and in vitro gene transfection efficiencies of polyplexes reconstituted after powder production than PAsp(DET)-based dry gene powder. From an in vitro inhalation study using an Andersen cascade impactor, it was demonstrated that the addition of l-leucine could markedly improve the inhalation performance of dry powders prepared by SFD. Following pulmonary delivery to mice, both PAsp(DET)- and PEG-PAsp(DET)-based dry gene powders could achieve higher gene transfection efficiencies in the lungs compared with a chitosan-based dry gene powder previously reported by us. PMID:26343708

  14. Mineralization of carbon and nitrogen from freeze- and over-dried plant material added to soil

    SciT

    Moorhead, K.K.; Graetz, D.A.; Reddy, K.R.

    Drying organic material before soil incorporation is a common procedure used in mineralization or decomposition studies. A laboratory study was conducted to determine the effect of drying methods on plant C and N and associated mineralization patterns in soil. Freeze- and oven-dried water hyacinth (Eichhornia crassipes (Mart) Solms) was added to a Kendrick soil (loamy, siliceous, hyperthermic Arenic Paleudults) at a rate of 5 g kg{sup {minus}1} and incubated in the dark at 27{degree}C for 90 d. Oven drying in paper bags significantly increased the lignin content and decreased the mineral content of the plant material compared to freeze drying.more » The total C and N was not significantly different for the two materials. The mineralization of C from freeze-dried plant material was more rapid during the initial stage of decomposition and remained significantly higher throughout the incubation. At 90 d, 50, and 41% of the plant C had evolved as CO{sub 2} for the freeze- and oven-dried plant material, respectively. Mineralization of {sup 15}N from the plant material accounted for 33% of the applied N of the freeze-dried material and 23% of the applied N of the oven-dried material. Nitrogen mineralization and CO{sub 2} evolution were linearly correlated (r=0.998) for the oven-dried plant material, but less correlated (r=0.770) for the freeze-dried material.« less

  15. Freeze-drying process monitoring using a cold plasma ionization device.

    PubMed

    Mayeresse, Y; Veillon, R; Sibille, P H; Nomine, C

    2007-01-01

    A cold plasma ionization device has been designed to monitor freeze-drying processes in situ by monitoring lyophilization chamber moisture content. This plasma device, which consists of a probe that can be mounted directly on the lyophilization chamber, depends upon the ionization of nitrogen and water molecules using a radiofrequency generator and spectrometric signal collection. The study performed on this probe shows that it is steam sterilizable, simple to integrate, reproducible, and sensitive. The limitations include suitable positioning in the lyophilization chamber, calibration, and signal integration. Sensitivity was evaluated in relation to the quantity of vials and the probe positioning, and correlation with existing methods, such as microbalance, was established. These tests verified signal reproducibility through three freeze-drying cycles. Scaling-up studies demonstrated a similar product signature for the same product using pilot-scale and larger-scale equipment. On an industrial scale, the method efficiently monitored the freeze-drying cycle, but in a larger industrial freeze-dryer the signal was slightly modified. This was mainly due to the positioning of the plasma device, in relation to the vapor flow pathway, which is not necessarily homogeneous within the freeze-drying chamber. The plasma tool is a relevant method for monitoring freeze-drying processes and may in the future allow the verification of current thermodynamic freeze-drying models. This plasma technique may ultimately represent a process analytical technology (PAT) approach for the freeze-drying process.

  16. Effects of annealing on the physical properties of therapeutic proteins during freeze drying process.

    PubMed

    Lim, Jun Yeul; Lim, Dae Gon; Kim, Ki Hyun; Park, Sang-Koo; Jeong, Seong Hoon

    2018-02-01

    Effects of annealing steps during the freeze drying process on etanercept, model protein, were evaluated using various analytical methods. The annealing was introduced in three different ways depending on time and temperature. Residual water contents of dried cakes varied from 2.91% to 6.39% and decreased when the annealing step was adopted, suggesting that they are directly affected by the freeze drying methods Moreover, the samples were more homogenous when annealing was adopted. Transition temperatures of the excipients (sucrose, mannitol, and glycine) were dependent on the freeze drying steps. Size exclusion chromatography showed that monomer contents were high when annealing was adopted and also they decreased less after thermal storage at 60°C. Dynamic light scattering results exhibited that annealing can be helpful in inhibiting aggregation and that thermal storage of freeze-dried samples preferably induced fragmentation over aggregation. Shift of circular dichroism spectrum and of the contents of etanercept secondary structure was observed with different freeze drying steps and thermal storage conditions. All analytical results suggest that the physicochemical properties of etanercept formulation can differ in response to different freeze drying steps and that annealing is beneficial for maintaining stability of protein and reducing the time of freeze drying process. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Protection of polyphenols in blueberry juice by vacuum-assisted block freeze concentration.

    PubMed

    Orellana-Palma, Patricio; Petzold, Guillermo; Pierre, Lissage; Pensaben, José Manuel

    2017-11-01

    Block freeze concentration allows produces high-quality cryoconcentrates with important protection of valuable components from fresh fruit juices. The aim of this study was to investigate the use of vacuum-assisted block freeze concentration under different experimental conditions to protect polyphenols in the elaboration of concentrated blueberry juice. Fresh blueberry juice was radial or unidirectional frozen at -20 and -80 °C for 12 h and vacuum process was performed at 80 kPa during 120 min. Results showed a significant solute increased in the concentrated fraction in all treatments, and the best treatment was - 20 °C/unidirectional with a value of ≈63 °Brix, equivalent to an increase of 3.8 times in the total polyphenol content (76% of retention). The color of concentrated samples was darker than the initial sample, with ΔE* values of >25 CIELab units in all treatments. The vacuum-assisted block freeze concentrations was an effective technology for protecting polyphenols and obtain a concentrated with a higher concentration of solids from blueberry juice, as well as interesting values of process parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Overview of High Power Vacuum Dry RF Load Designs

    SciT

    Krasnykh, Anatoly

    2015-08-27

    A specific feature of RF linacs based on the pulsed traveling wave (TW) mode of operation is that only a portion of the RF energy is used for the beam acceleration. The residual RF energy has to be terminated into an RF load. Higher accelerating gradients require higher RF sources and RF loads, which can stably terminate the residual RF power. RF feeders (from the RF source though the accelerating section to the load) are vacuumed to transmit multi-megawatt high power RF. This overview will outline vacuumed RF loads only. A common method to terminate multi-MW RF power is tomore » use circulated water (or other liquid) as an absorbing medium. A solid dielectric interface (a high quality ceramic) is required to separate vacuum and liquid RF absorber mediums. Using such RF load approaches in TW linacs is troubling because there is a fragile ceramic window barrier and a failure could become catastrophic for linac vacuum and RF systems. Traditional loads comprising of a ceramic disk have limited peak and average power handling capability and are therefore not suitable for high gradient TW linacs. This overview will focus on ''vacuum dry'' or ''all-metal'' loads that do not employ any dielectric interface between vacuum and absorber. The first prototype is an original design of RF loads for the Stanford Two-Mile Accelerator.« less

  19. Development of freeze-dried miyeokguk, Korean seaweed soup, as space food sterilized by irradiation

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Park, Jin-Gyu; Kim, Jae-Hun; Choi, Jong-Il; Ahn, Dong-Hyun; Hao, Chen; Lee, Ju-Woon

    2012-08-01

    The purpose of this study was to evaluate microbial populations, Hunter's color values (L*, a*, b*) and the sensory quality of freeze-dried miyeokguk, Korean seaweed soup, in order to use it as space food. Microorganisms were not detected in non-irradiated freeze-dried miyeokguk within the detection limit of 1.00 log CFU/g. However, the microbial population in rehydrated miyeokguk was 7.01 log CFU/g after incubation at 35 °C for 48 h, indicating that freeze-dried miyeokguk was not sterilized by heat treatment during the preparation process. Bacteria in the freeze-dried miyeokguk were tentatively identified as Bacillus cereus, B. subtilis, Enterobacter hormaechei, and Ancinetobacter genomosp. using the 16S rDNA sequencing. In samples that were gamma-irradiated above 10 kGy, it was confirmed that all microorganisms were inactivated. Hunter's color values of the samples irradiated at doses less than 10 kGy were not significantly altered from their baseline appearance (p>0.05). Sensory evaluation showed that preference scores in all sensory properties decreased when freeze-dried miyeokguk was irradiated at doses greater than 10 kGy. Therefore, the results of this study suggest that gamma irradiation at 10 kGy is sufficient to sterilize freeze-dried miyeokguk without significant deterioration in the sensory quality, and thus, the freeze-dried and irradiated miyeokguk at 10 kGy fulfills the microbiological requirements as space food.

  20. Mechanisms of deterioration of nutrients. [freeze drying methods for space flight food

    NASA Technical Reports Server (NTRS)

    Karel, M.; Flink, J. M.

    1974-01-01

    Methods are reported by which freeze dried foods of improved quality will be produced. The applicability of theories of flavor retention has been demonstrated for a number of food polymers, both proteins and polysacchardies. Studies on the formation of structures during freeze drying have been continued for emulsified systems. Deterioration of organoleptic quality of freeze dried foods due to high temperature heating has been evaluated and improved procedures developed. The influence of water activity and high temperature on retention of model flavor materials and browning deterioration has been evaluated for model systems and food materials.

  1. Stability of pseudorabies virus during freeze-drying and storage: effect of suspending media.

    PubMed Central

    Scott, E M; Woodside, W

    1976-01-01

    The effect of suspending media on the stability of pseudorabies virus upon freeze-drying and subsequent storage was studied. A variety of media was tested, including: sodium glutamate; sucrose; lactose; lactalbumin hydrolysate; peptone; a combination of sucrose, dextran, and glutamate; and various combinations of sucrose, glutamate, and potassium phosphates. Suspending media containing glutamate, either alone or in combination with sucrose and either dextran or phosphates, afforded the greatest degree of protection during the freeze-drying process and upon storage. Some possible functions of these additives in preventing injury to the virus during freezing and drying have been suggested. PMID:182713

  2. Ice nucleation temperature influences recovery of activity of a model protein after freeze drying.

    PubMed

    Cochran, Teresa; Nail, Steven L

    2009-09-01

    The objective of this study was to determine whether a relationship exists between ice nucleation temperature and recovery of activity of a model protein, lactate dehydrogenase, after freeze drying. Aqueous buffer systems containing 50 microg/mL of protein were frozen in vials with externally mounted thermocouples on the shelf of a freeze dryer, then freeze dried. Various methods were used to establish a wide range of ice nucleation temperatures. An inverse relationship was found between the extent of supercooling during freezing and recovery of activity in the reconstituted solution. The data are consistent with a mechanism of inactivation resulting from adsorption of protein at the ice/freeze-concentrate interface during the freezing process.

  3. Experimental and numerical investigations on freeze-drying of porous media with prebuilt porosity

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Yang, Jing; Hu, Dapeng; Pan, Yanqiu; Wang, Shihao; Chen, Guohua

    2018-05-01

    Freeze-drying of initially porous frozen material was investigated aimed at improving the process economics by reducing drying time and raising productivity. Experimental results showed that freeze-drying can be significantly enhanced by the frozen material with prebuilt porosity, and about 31% of drying time can be saved compared with the conventionally solid frozen material under the tested operating conditions. A multiphase transport model was formulated based on the local mass non-equilibrium assumption. Numerical results showed excellent agreements between measured and predicted drying curves. Analyses of saturation and temperature profiles displayed that volumetric sublimation-desorption can occur for the initially porous frozen material.

  4. Model for heat and mass transfer in freeze-drying of pellets.

    PubMed

    Trelea, Ioan Cristian; Passot, Stéphanie; Marin, Michèle; Fonseca, Fernanda

    2009-07-01

    Lyophilizing frozen pellets, and especially spray freeze-drying, have been receiving growing interest. To design efficient and safe freeze-drying cycles, local temperature and moisture content in the product bed have to be known, but both are difficult to measure in the industry. Mathematical modeling of heat and mass transfer helps to determine local freeze-drying conditions and predict effects of operation policy, and equipment and recipe changes on drying time and product quality. Representative pellets situated at different positions in the product slab were considered. One-dimensional transfer in the slab and radial transfer in the pellets were assumed. Coupled heat and vapor transfer equations between the temperature-controlled shelf, the product bulk, the sublimation front inside the pellets, and the chamber were established and solved numerically. The model was validated based on bulk temperature measurement performed at two different locations in the product slab and on partial vapor pressure measurement in the freeze-drying chamber. Fair agreement between measured and calculated values was found. In contrast, a previously developed model for compact product layer was found inadequate in describing freeze-drying of pellets. The developed model represents a good starting basis for studying freeze-drying of pellets. It has to be further improved and validated for a variety of product types and freeze-drying conditions (shelf temperature, total chamber pressure, pellet size, slab thickness, etc.). It could be used to develop freeze-drying cycles based on product quality criteria such as local moisture content and glass transition temperature.

  5. Freezing and drying effects on potential plant contributions to phosphorus in runoff.

    PubMed

    Roberson, Tiffany; Bundy, Larry G; Andraski, Todd W

    2007-01-01

    Phosphorus (P) in runoff from landscapes can promote eutrophication of natural waters. Soluble P released from plant material can contribute significant amounts of P to runoff particularly after plant freezing or drying. This study was conducted to evaluate P losses from alfalfa or grass after freezing or drying as potential contributors to runoff P. Alfalfa (Medicago sativa L.) and grass (principally, Agropyron repens L.) plant samples were subjected to freezing and drying treatments to determine P release. Simulated rainfall runoff and natural runoff from established alfalfa fields and a grass waterway were collected to study P contributions from plant tissue to runoff. The effects of freezing and drying on P released from plant tissue were simulated by a herbicide treatment in selected experiments. Soluble reactive P (SP) extracted from alfalfa and grass samples was markedly increased by freezing or drying. In general, SP extracted from plant samples increased in the order fresh < frozen < frozen/thawed < dried, and averaged 1, 8, 14, and 26% of total P in alfalfa, respectively. Soluble reactive P extracted from alfalfa after freezing or drying increased with increasing soil test P (r(2) = 0.64 to 0.68), suggesting that excessive soil P levels increased the risk of plant P contributions to runoff losses. In simulated rainfall studies, paraquat (1,1'-dimethyl-4, 4''-bipyridinium ion) treatment of alfalfa increased P losses in runoff, and results suggested that this treatment simulated the effects of drying on plant P loss. In contrast to the simulated rainfall results, natural runoff studies over 2 yr did not show higher runoff P losses that could be attributed to P from alfalfa. Actual P losses likely depend on the timing and extent of plant freezing and drying and of precipitation events after freezing.

  6. Physicochemical interaction mechanism between nanoparticles and tetrasaccharides (stachyose) during freeze-drying.

    PubMed

    Kamiya, Seitaro; Nakashima, Kenichiro

    2017-12-01

    Nanoparticle suspensions are thermodynamically unstable and subject to aggregation. Freeze-drying on addition of saccharides is a useful method for preventing aggregation. In the present study, tetrasaccharides (stachyose) was employed as an additive. In addition, we hypothesize the interactive mechanism between stachyose and the nanoparticles during freeze-drying for the first time. The mean particle size of the rehydrated freeze-dried stachyose-containing nanoparticles (104.7 nm) was similar to the initial particle size before freeze-drying (76.8 nm), indicating that the particle size had been maintained. The mean particle size of the rehydrated normal-dried stachyose-containing nanoparticles was 222.2 nm. The powder X-ray diffraction of the freeze-dried stachyose-containing nanoparticles revealed a halo pattern. The powder X-ray diffraction of the normally dried stachyose-containing nanoparticles produced mainly a halo pattern and a partial peak. These results suggest an interaction between the nanoparticles and stachyose, and that this relationship depends on whether the mixture is freeze-dried or dried normally. In the case of normal drying, although most molecules cannot move rapidly thereby settling irregularly, some stachyose molecules can arrange regularly leading to some degree of crystallization and potentially some aggregation. In contrast, during freeze-drying, the moisture sublimed, while the stachyose molecules and nanoparticles were immobilized in the ice. After sublimation, stachyose remained in the space occupied by water and played the role of a buffer material, thus preventing aggregation.

  7. Toward intradermal vaccination: preparation of powder formulations by collapse freeze-drying.

    PubMed

    Etzl, Elsa E; Winter, Gerhard; Engert, Julia

    2014-03-01

    Intradermal powder immunization is an emerging technique in vaccine delivery. The purpose of this study was to generate powder particles for intradermal injection by freeze-drying and subsequent cryo-milling. Two different freeze-drying protocols were compared, a moderate freeze-drying cycle and an aggressive freeze-drying cycle, which induced a controlled collapse of the sugar matrix. Ovalbumin served as model antigen. The influence of collapse drying and cryo-milling on particle morphology and protein stability was investigated. Cryo-milling generated irregularly shaped particles of size 20-70 µm. The recovery of soluble monomer of ovalbumin was not changed during freeze-drying and after cryo-milling, or after 12 months of storage at 2-8 °C. A slight increase in higher molecular weight aggregates was found in formulations containing the polymer dextran after 12 months of storage at 50 °C. Light obscuration measurements showed an increase in cumulative particle counts after cryo-milling that did not further increase during storage at 2-8 °C for 12 months. The applicability of the cryo-milling process to other therapeutic proteins was shown using recombinant human granulocyte-colony stimulating factor. Collapse freeze-drying and subsequent cryo-milling allows the generation of particles suitable for intradermal powder injection.

  8. Continuous measurement of drying rate of crystalline and amorphous systems during freeze-drying using an in situ microbalance technique.

    PubMed

    Roth, C; Winter, G; Lee, G

    2001-09-01

    The use of a novel microbalance (Christ) technique to monitor continuously the weight loss of a vial standing on a shelf of a freeze-dryer has been investigated. The drying rates of the following aqueous solutions were measured during the primary drying phase of a complete freeze-drying cycle: sucrose (75 mg/mL, 2.5-mL fill volume), sucrose and phenylalanine (1:0.2 by weight, 75 mg/mL, 2.5-mL fill volume), and mannitol (75mg/mL, 2.5-mL fill volume). The microbalance yields the cumulative water loss, m(cu) in grams, and the momentary drying rate, Deltam(cu)/Deltat in mg/10 min, of the frozen cake. The momentary drying rate curves were especially useful for examining how Deltam(cu)/Deltat changes with time during primary drying. Initially, Deltam(cu)/Deltat rises to a sharp maximum and then decreases in a fashion depending on shelf temperature, chamber pressure, and the nature of the substance being dried. Different drying behavior was observed for the sucrose and sucrose/phenylalanine systems, which was attributed to the presence of crystalline phenylalanine in the amorphous sucrose. At low shelf-temperature (-24 degrees C) the crystalline mannitol showed lower Deltam(cu)/Deltat than with either sucrose or sucrose/phenylalanine. The balance could also detect differences in Deltam(cu)/Deltat when using different freezing protocols. "Slow" and "moderate" freezing protocols gave similar drying behavior, but "rapid" freezing in liquid nitrogen produced greatly altered drying rate and internal cake morphology. The balance also could be used to detect the endpoint of primary drying. Different endpoint criteria and their influence on final dried cake properties were examined. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association

  9. Sperm Preservation by Freeze-Drying for the Conservation of Wild Animals

    PubMed Central

    Kaneko, Takehito; Ito, Hideyuki; Sakamoto, Hidefusa; Onuma, Manabu; Inoue-Murayama, Miho

    2014-01-01

    Sperm preservation is a useful technique for the maintenance of biological resources in experimental and domestic animals, and in wild animals. A new preservation method has been developed that enables sperm to be stored for a long time in a refrigerator at 4°C. Sperm are freeze-dried in a solution containing 10 mM Tris and 1 mM EDTA. Using this method, liquid nitrogen is not required for the storage and transportation of sperm. We demonstrate that chimpanzee, giraffe, jaguar, weasel and the long-haired rat sperm remain viable after freeze-drying. In all species, pronuclei were formed after the injection of freeze-dried sperm into the mouse oocytes. Although preliminary, these results may be useful for the future establishment of “freeze-drying zoo” to conserve wild animals. PMID:25409172

  10. Sperm preservation by freeze-drying for the conservation of wild animals.

    PubMed

    Kaneko, Takehito; Ito, Hideyuki; Sakamoto, Hidefusa; Onuma, Manabu; Inoue-Murayama, Miho

    2014-01-01

    Sperm preservation is a useful technique for the maintenance of biological resources in experimental and domestic animals, and in wild animals. A new preservation method has been developed that enables sperm to be stored for a long time in a refrigerator at 4 °C. Sperm are freeze-dried in a solution containing 10 mM Tris and 1 mM EDTA. Using this method, liquid nitrogen is not required for the storage and transportation of sperm. We demonstrate that chimpanzee, giraffe, jaguar, weasel and the long-haired rat sperm remain viable after freeze-drying. In all species, pronuclei were formed after the injection of freeze-dried sperm into the mouse oocytes. Although preliminary, these results may be useful for the future establishment of "freeze-drying zoo" to conserve wild animals.

  11. Emerging freeze-drying process development and scale-up issues.

    PubMed

    Patel, Sajal Manubhai; Pikal, Michael J

    2011-03-01

    Although several guidelines do exist for freeze-drying process development and scale-up, there are still a number of issues that require additional attention. The objective of this review article is to discuss some emerging process development and scale-up issue with emphasis on effect of load condition and freeze-drying in novel container systems such as syringes, Lyoguard trays, ampoules, and 96-well plates. Understanding the heat and mass transfer under different load conditions and for freeze-drying in these novel container systems will help in developing a robust freeze-drying process which is also easier to scale-up. Further research and development needs in these emerging areas have also been addressed. © 2011 American Association of Pharmaceutical Scientists

  12. The human milk oligosaccharides are not affected by pasteurization and freeze-drying.

    PubMed

    Hahn, Won-Ho; Kim, Jaehan; Song, Seunghyun; Park, Suyeon; Kang, Nam Mi

    2017-11-06

    Human milk oligosaccharides (HMOs) are known as important factors in neurologic and immunologic development of neonates. Moreover, freeze-drying seems to be a promising storage method to improve the processes of human milk banks. However, the effects of pasteurization and freeze-drying on HMOs were not evaluated yet. The purpose of this study is to analyze and compare the HMOs profiles of human milk collected before and after the pasteurization and freeze-drying. Totally nine fresh human milk samples were collected from three healthy mothers at the first, second, and third week after delivery. The samples were treated with Holder pasteurization and freeze-drying. HMOs profiles were analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry and compared between samples collected before and after the treatments. Human milk samples showed significantly different HMO patterns between mothers. However, HMOs were not affected by lactation periods within 3 weeks after delivery (r 2  = 0.972-0.999, p < .001). Moreover, both of pasteurization and freeze-drying were found not to affect HMO patterns in a correlation analysis (r 2  = 0.989-0.999, p < .001). HMO patterns were found not to be affected by pasteurization and freeze-drying of donor milks. We hope that introducing freeze-drying to the human milk banks would be encouraged by the present study. However, the storage length without composition changes of HMOs after freeze-drying needs to be evaluated in the further studies.

  13. Infrared Thermography for Monitoring of Freeze-Drying Processes: Instrumental Developments and Preliminary Results

    PubMed Central

    Emteborg, Håkan; Zeleny, Reinhard; Charoud-Got, Jean; Martos, Gustavo; Lüddeke, Jörg; Schellin, Holger; Teipel, Katharina

    2014-01-01

    Coupling an infrared (IR) camera to a freeze dryer for on-line monitoring of freeze-drying cycles is described for the first time. Normally, product temperature is measured using a few invasive Pt-100 probes, resulting in poor spatial resolution. To overcome this, an IR camera was placed on a process-scale freeze dryer. Imaging took place every 120 s through a Germanium window comprising 30,000 measurement points obtained contact-free from −40°C to 25°C. Results are presented for an empty system, bulk drying of cheese slurry, and drying of 1 mL human serum in 150 vials. During freezing of the empty system, differences of more than 5°C were measured on the shelf. Adding a tray to the empty system, a difference of more than 8°C was observed. These temperature differences probably cause different ice structures affecting the drying speed during sublimation. A temperature difference of maximum 13°C was observed in bulk mode during sublimation. When drying in vials, differences of more than 10°C were observed. Gradually, the large temperature differences disappeared during secondary drying and products were transformed into uniformly dry cakes. The experimental data show that the IR camera is a highly versatile on-line monitoring tool for different kinds of freeze-drying processes. © 2014 European Union 103:2088–2097, 2014 PMID:24902839

  14. Infrared thermography for monitoring of freeze-drying processes: instrumental developments and preliminary results.

    PubMed

    Emteborg, Håkan; Zeleny, Reinhard; Charoud-Got, Jean; Martos, Gustavo; Lüddeke, Jörg; Schellin, Holger; Teipel, Katharina

    2014-07-01

    Coupling an infrared (IR) camera to a freeze dryer for on-line monitoring of freeze-drying cycles is described for the first time. Normally, product temperature is measured using a few invasive Pt-100 probes, resulting in poor spatial resolution. To overcome this, an IR camera was placed on a process-scale freeze dryer. Imaging took place every 120 s through a Germanium window comprising 30,000 measurement points obtained contact-free from -40 °C to 25 °C. Results are presented for an empty system, bulk drying of cheese slurry, and drying of 1 mL human serum in 150 vials. During freezing of the empty system, differences of more than 5 °C were measured on the shelf. Adding a tray to the empty system, a difference of more than 8 °C was observed. These temperature differences probably cause different ice structures affecting the drying speed during sublimation. A temperature difference of maximum 13 °C was observed in bulk mode during sublimation. When drying in vials, differences of more than 10 °C were observed. Gradually, the large temperature differences disappeared during secondary drying and products were transformed into uniformly dry cakes. The experimental data show that the IR camera is a highly versatile on-line monitoring tool for different kinds of freeze-drying processes. © 2014 European Union.

  15. Effects of six substances on the growth and freeze-drying of Lactobacillus delbrueckii subsp. bulgaricus.

    PubMed

    Chen, He; Huang, Jie; Shi, Xiaoyu; Li, Yichao; Liu, Yu

    2017-01-01

    The efficacy of Lactobacillus delbrueckii subsp. bulgaricus as starter cultures for the dairy industry depends largely on the number of viable and active cells. Freeze-drying is the most convenient and successful method to preserve the bacterial cells. However, not all strains survived during freeze-drying. The effects of six substances including NaCl, sorbitol, mannitol, mannose, sodium glutamate, betaine added to the MRS medium on the growth and freeze-drying survival rate and viable counts of Lb. delbrueckii subsp. bulgaricus were studied through a single-factor test and Plackett-Burman design. Subsequently, the optimum freeze-drying conditions of Lb. delbrueckii subsp. bulgaricus were determined. Lb. delbrueckii subsp. bulgaricus survival rates were up to the maximum of 42.7%, 45.4%, 23.6%, while the concentrations of NaCl, sorbitol, sodium glutamate were 0.6%, 0.15%, 0.09%, respectively. In the optimum concentration, the viable counts in broth is 6.1, 6.9, 5.13 (×108 CFU/mL), respectively; the viable counts in freeze-drying power are 3.09, 5.2, 2.7 (×1010 CFU/g), respectively. Three antifreeze factors including NaCl, sorbitol, sodium glutamate have a positive effect on the growth and freeze-drying of Lb. delbrueckii subsp. bulgaricus. The results are beneficial for developing Lb. delbrueckii subsp. bulgaricus.

  16. Use of manometric temperature measurement (MTM) and SMART freeze dryer technology for development of an optimized freeze-drying cycle.

    PubMed

    Gieseler, Henning; Kramer, Tony; Pikal, Michael J

    2007-12-01

    This report provides, for the first time, a summary of experiments using SMART Freeze Dryer technology during a 9 month testing period. A minimum ice sublimation area of about 300 cm(2) for the laboratory freeze dryer, with a chamber volume 107.5 L, was found consistent with data obtained during previous experiments with a smaller freeze dryer (52 L). Good reproducibility was found for cycle design with different type of excipients, formulations, and vials used. SMART primary drying end point estimates were accurate in the majority of the experiments, but showed an over prediction of primary cycle time when the product did not fully achieve steady state conditions before the first MTM measurement was performed. Product resistance data for 5% sucrose mixtures at varying fill depths were very reproducible. Product temperature determined by SMART was typically in good agreement with thermocouple data through about 50% of primary drying time, with significant deviations occurring near the end of primary drying, as expected, but showing a bias much earlier in primary drying for high solid content formulations (16.6% Pfizer product) and polyvinylpyrrolidone (40 kDa) likely due to water "re-adsorption" by the amorphous product during the MTM test. (c) 2007 Wiley-Liss, Inc.

  17. Drying characteristics of pumpkin ( Cucurbita moschata) slices in convective and freeze dryer

    NASA Astrophysics Data System (ADS)

    Caliskan, Gulsah; Dirim, Safiye Nur

    2017-06-01

    This study was intended to determine the drying and rehydration kinetics of convective and freeze dried pumpkin slices (0.5 × 3.5 × 0.5 cm). A pilot scale tray drier (at 80 ± 2 °C inlet temperature, 1 m s-1 air velocity) and freeze drier (13.33 kPa absolute pressure, condenser temperature of -48 ± 2 °C) were used for the drying experiments. Drying curves were fitted to six well-known thin layer drying models. Nonlinear regression analysis was used to evaluate the parameters of the selected models by using statistical software SPSS 16.0 (SPSS Inc., USA). For the convective and freeze drying processes of pumpkin slices, the highest R2 values, and the lowest RMSE as well as χ2 values were obtained from Page model. The effective moisture diffusivity (Deff) of the convective and freeze dried pumpkin slices were obtained from the Fick's diffusion model, and they were found to be 2.233 × 10-7 and 3.040 × 10-9 m2s-1, respectively. Specific moisture extraction rate, moisture extraction rate, and specific energy consumption values were almost twice in freeze drying process. Depending on the results, moisture contents and water activity values of pumpkin slices were in acceptable limits for safe storage of products. The rehydration behaviour of [at 18 ± 2 and 100 ± 2 °C for 1:25, 1:50, 1:75, 1:100, and 1:125 solid:liquid ratios (w:w)] dried pumpkin slices was determined by Peleg's model with the highest R2. The highest total soluble solid loss of pumpkin slices was observed for the rehydration experiment which performed at 1:25 solid: liquid ratio (w:w). Rehydration ratio of freeze dried slices was found 2-3 times higher than convective dried slices.

  18. The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process.

    PubMed

    Grohganz, Holger; Lee, Yan-Ying; Rantanen, Jukka; Yang, Mingshi

    2013-04-15

    Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near-infrared spectroscopy in combination with multivariate analysis and further, results were verified with X-ray powder diffraction. It was seen that the prevalence of the mannitol polymorphic form shifted from β-mannitol to δ-mannitol with increasing protein concentration in freeze-dried formulations. In spray-dried formulations an increase in protein concentration resulted in a shift from β-mannitol to α-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying process in itself, rather than the temperature, that leads to the observed solid state changes. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Modelling and simulation of a moving interface problem: freeze drying of black tea extract

    NASA Astrophysics Data System (ADS)

    Aydin, Ebubekir Sıddık; Yucel, Ozgun; Sadikoglu, Hasan

    2017-06-01

    The moving interface separates the material that is subjected to the freeze drying process as dried and frozen. Therefore, the accurate modeling the moving interface reduces the process time and energy consumption by improving the heat and mass transfer predictions during the process. To describe the dynamic behavior of the drying stages of the freeze-drying, a case study of brewed black tea extract in storage trays including moving interface was modeled that the heat and mass transfer equations were solved using orthogonal collocation method based on Jacobian polynomial approximation. Transport parameters and physical properties describing the freeze drying of black tea extract were evaluated by fitting the experimental data using Levenberg-Marquardt algorithm. Experimental results showed good agreement with the theoretical predictions.

  20. Evaluation of Heat Flux Measurement as a New Process Analytical Technology Monitoring Tool in Freeze Drying.

    PubMed

    Vollrath, Ilona; Pauli, Victoria; Friess, Wolfgang; Freitag, Angelika; Hawe, Andrea; Winter, Gerhard

    2017-05-01

    This study investigates the suitability of heat flux measurement as a new technique for monitoring product temperature and critical end points during freeze drying. The heat flux sensor is tightly mounted on the shelf and measures non-invasively (no contact with the product) the heat transferred from shelf to vial. Heat flux data were compared to comparative pressure measurement, thermocouple readings, and Karl Fischer titration as current state of the art monitoring techniques. The whole freeze drying process including freezing (both by ramp freezing and controlled nucleation) and primary and secondary drying was considered. We found that direct measurement of the transferred heat enables more insights into thermodynamics of the freezing process. Furthermore, a vial heat transfer coefficient can be calculated from heat flux data, which ultimately provides a non-invasive method to monitor product temperature throughout primary drying. The end point of primary drying determined by heat flux measurements was in accordance with the one defined by thermocouples. During secondary drying, heat flux measurements could not indicate the progress of drying as monitoring the residual moisture content. In conclusion, heat flux measurements are a promising new non-invasive tool for lyophilization process monitoring and development using energy transfer as a control parameter. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Microplate freeze-dried cyanobacterial bioassay for fresh-waters environmental monitoring.

    PubMed

    Martín-Betancor, Keila; Durand, Marie-José; Thouand, Gérald; Leganés, Francisco; Fernández-Piñas, Francisca; Rodea-Palomares, Ismael

    2017-12-01

    Microorganisms have been very useful in environmental monitoring due to their constant sensing of the surrounding environment, their easy maintenance and low cost. Some freeze-dried toxicity kits based on naturally bioluminescent bacteria are commercially available and commonly used to assess the toxicity of environmental samples such as Microtox (Aliivibrio fischeri) or ToxScreen (Photobacterium leiognathi), however, due to the marine origin of these bacteria, they could not be the most appropriate for fresh-waters monitoring. Cyanobacteria are one of the most representative microorganisms of aquatic environments, and are well suited for detecting contaminants in aqueous samples. This study presents the development and application of the first freeze-dried cyanobacterial bioassay for fresh-water contaminants detection. The effects of different cell growth phases, cryoprotectant solutions, freezing protocols, rehydration solutions and incubation conditions methods were evaluated and the best combination of these parameters for freeze-drying was selected. The study includes detailed characterization of sensitivity towards reference pollutants, as well as, comparison with the standard assays. Moreover, long-term viability and sensitivity were evaluated after 3 years of storage. Freeze-dried cyanobacteria showed, in general, higher sensitivity than the standard assays and viability of the cells remained after 3 years of storage. Finally, the validation of the bioassay using a wastewater sample was also evaluated. Freeze-drying of cyanobacteria in 96-well plates presents a simple, fast and multi-assay method for environmental monitoring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Effects of Freeze-Dried Vegetable Products on the Technological Process and the Quality of Dry Fermented Sausages.

    PubMed

    Eisinaite, Viktorija; Vinauskiene, Rimante; Viskelis, Pranas; Leskauskaite, Daiva

    2016-09-01

    The aim of this study was to compare the chemical composition of freeze-dried vegetable powders: celery, celery juice, parsnip and leek. The effect of different freeze-dried vegetables onto the ripening process and the properties of dry fermented sausages was also evaluated. Vegetable products significantly (p < 0.05) differed in their chemical composition: celery products contained higher amounts of nitrates, total phenolic compounds and lower amounts of sucrose, parsnip had higher concentration of proteins, leek was rich in fat. The analysis of pH, water activity, lactic acid bacteria, coagulase-positive staphylococci and coliforms content showed that the incorporation of freeze-dried vegetables had no negative effect on the fermentation and ripening process of dry fermented sausages. In addition, the color parameters for sausages with the added lyophilised celery products were considerable (p < 0.05) more stable during these processes. At the end of the ripening process the sausages made with lyophilised celery juice were characterised by higher lightness and lower hardness than those made with the addition of other vegetable products and control. Freeze-dried celery, celery juice, parsnip and leek have some potential for the usage as a functional ingredient or as a source for indirect addition of nitrate in the production of fermented sausages. © 2016 Institute of Food Technologists®

  3. Determination of the dried product resistance variability and its influence on the product temperature in pharmaceutical freeze-drying.

    PubMed

    Scutellà, Bernadette; Trelea, Ioan Cristian; Bourlès, Erwan; Fonseca, Fernanda; Passot, Stephanie

    2018-07-01

    During the primary drying step of the freeze-drying process, mass transfer resistance strongly affects the product temperature, and consequently the final product quality. The main objective of this study was to evaluate the variability of the mass transfer resistance resulting from the dried product layer (R p ) in a manufacturing batch of vials, and its potential effect on the product temperature, from data obtained in a pilot scale freeze-dryer. Sublimation experiments were run at -25 °C and 10 Pa using two different freezing protocols: with spontaneous or controlled ice nucleation. Five repetitions of each condition were performed. Global (pressure rise test) and local (gravimetric) methods were applied as complementary approaches to estimate R p . The global method allowed to assess variability of the evolution of R p with the dried layer thickness between different experiments whereas the local method informed about R p variability at a fixed time within the vial batch. A product temperature variability of approximately ±4.4 °C was defined for a product dried layer thickness of 5 mm. The present approach can be used to estimate the risk of failure of the process due to mass transfer variability when designing freeze-drying cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Microbial analysis and survey test of gamma-irradiated freeze-dried fruits for patient's food

    NASA Astrophysics Data System (ADS)

    Park, Jae-Nam; Sung, Nak-Yun; Byun, Eui-Hong; Byun, Eui-Baek; Song, Beom-Seok; Kim, Jae-Hun; Lee, Kyung-A.; Son, Eun-Joo; Lyu, Eun-Soon

    2015-06-01

    This study examined the microbiological and organoleptic qualities of gamma-irradiated freeze-dried apples, pears, strawberries, pineapples, and grapes, and evaluated the organoleptic acceptability of the sterilized freeze-dried fruits for hospitalized patients. The freeze-dried fruits were gamma-irradiated at 0, 1, 2, 3, 4, 5, 10, 12, and 15 kGy, and their quality was evaluated. Microorganisms were not detected in apples after 1 kGy, in strawberries and pears after 4 kGy, in pineapples after 5 kGy, and in grapes after 12 kGy of gamma irradiation. The overall acceptance score, of the irradiated freeze-dried fruits on a 7-point scale at the sterilization doses was 5.5, 4.2, 4.0, 4.1, and 5.1 points for apples, strawberries, pears, pineapples, and grapes, respectively. The sensory survey of the hospitalized cancer patients (N=102) resulted in scores of 3.8, 3.7, 3.9, 3.9, and 3.7 on a 5-point scale for the gamma-irradiated freeze-dried apples, strawberries, pears, pineapples, and grapes, respectively. The results suggest that freeze-dried fruits can be sterilized with a dose of 5 kGy, except for grapes, which require a dose of 12 kGy, and that the organoleptic quality of the fruits is acceptable to immuno-compromised patients. However, to clarify the microbiological quality and safety of freeze-dried fruits should be verified by plating for both aerobic and anaerobic microorganisms.

  5. Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-09-15

    Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717 mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4 °C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3 °C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules.

  6. The physico-chemical basis for the freeze-drying process.

    PubMed

    MacKenzie, A P

    1976-10-01

    To the extent that the final form and quality of a freeze-dried product depends on the way the freeze-drying is conducted, an understanding of the many factors involved is most important. The numerous effects of the design and mode of operation of the freeze-drying equipment on the course of the process need to be known, as do the properties intrinsic to the material to be freeze-dried. Much can be learned and predicted from the study of the "supplemented phase diagram", a series of experimental plots describing the equilibrium and the non-equilibrium phase behavior of the system in question. Such diagrams map and distinguish eutectic and amorphous phase behavior. Further information is available from gravimetric studies allowing the construction of "desorption isotherms", the plots describing the loss of sorbed water accompanying the sublimation of ice, frequently termed "secondary drying". These plots relate the water retained by the product to the "water activity", or relative humidity at different temperatures. Observations in the freeze-drying microscope contribute additional information, in that they reveal the actual course of the process at the microscopic level. These and other laboratory findings facilitate the analysis and comparison of pilot-plant and commercical scale processing experiences. Where scientific and engineering factors appear to interrelate, the nature and extent of the interdependence can often be determined.

  7. The Freeze-Drying of Wet and Waterlogged Materials from Archaeological Excavations

    ERIC Educational Resources Information Center

    Watson, Jacqui

    2004-01-01

    Large quantities of wood and leather have been found in the waterlogged layers on archaeological excavations. Centuries of burial, however, have left these materials in a very degraded and vulnerable state such that if they dry out they will fall apart. This paper discusses the physics behind the freeze-drying techniques that allow the…

  8. Controlled ice nucleation in the field of freeze-drying: fundamentals and technology review.

    PubMed

    Geidobler, R; Winter, G

    2013-10-01

    In the scientific community as well as in commercial freeze-drying, controlled ice nucleation has received a lot of attention because increasing the ice nucleation temperature can significantly reduce primary drying duration. Furthermore, controlled ice nucleation enables to reduce the randomness of the ice nucleation temperature, which can be a serious scale-up issue during process development. In this review, fundamentals of ice nucleation in the field of freeze-drying are presented. Furthermore, the impact of controlled ice nucleation on product qualities is discussed, and methods to achieve controlled ice nucleation are presented. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Effect of freeze-drying and oven-drying on volatiles and phenolics composition of grape skin.

    PubMed

    de Torres, C; Díaz-Maroto, M C; Hermosín-Gutiérrez, I; Pérez-Coello, M S

    2010-02-15

    Grape skins are the part of the fruit with the highest amount of volatile and polyphenolic compounds. Volatile compounds give the fruit and other grape derivatives their flavour. Polyphenolic compounds are responsible for the colour of the fruit, juice and wine, and also act as very important natural antioxidant compounds. Dehydration is a method used to prevent the damage of these compounds over time. Nevertheless, in the case of volatile compounds, removing water can cause compound degradation or the evaporation of such compounds. This work studied two drying methods, freeze-drying and oven-drying, at 60 degrees C, as skin preservation methods. The skins from two grape varieties, Carménère and Cabernet Sauvignon, were dried. Many volatile compounds, which are of interest in the aroma profile, were identified in both varieties as terpenes (linalool, etc.), sesquiterpenes (farnesol), norisoprenoids (vitispirane, etc.), C(6) alcohols (1-hexanol, etc.), etc., and their amount decreased significantly with the oven-drying method, in contrast to the freeze-drying method. Both phenolic compounds, anthocyanins and flavonols, were identified in fresh and dehydrated samples, thus resulting in the freeze-drying method being less aggressive than oven-drying methods. Copyright 2009 Elsevier B.V. All rights reserved.

  10. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    PubMed

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-04

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects.

  11. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives

    PubMed Central

    2015-01-01

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm2 provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects. PMID:26457864

  12. Mass transfer parameters of celeriac during vacuum drying

    NASA Astrophysics Data System (ADS)

    Beigi, Mohsen

    2017-04-01

    An accurate prediction of moisture transfer parameters is very important for efficient mass transfer analysis, accurate modelling of drying process, and better designing of new dryers and optimization of existing drying process. The present study aimed to investigate the influence of temperature (e.g., 55, 65 and 75 °C) and chamber pressure (e.g., 0.1, 3, 7, 10, 13 and 17 kPa) on effective diffusivity and convective mass transfer coefficient of celeriac slices during vacuum drying. The obtained Biot number indicated that the moisture transfer in the celeriac slices was controlled by both internal and external resistance. The effective diffusivity obtained to be in the ranges of 7.5231 × 10-10-3.8015 × 10-9 m2 s-1. The results showed that the diffusivity increased with increasing temperature and decreasing pressure. The mass transfer coefficient values varied from 4.6789 × 10-7 to 1.0059 × 10-6 m s-1, and any increment in drying temperature and pressure caused an increment in the coefficient.

  13. Freeze-dried spermatozoa: An alternative biobanking option for endangered species.

    PubMed

    Anzalone, Debora Agata; Palazzese, Luca; Iuso, Domenico; Martino, Giuseppe; Loi, Pasqualino

    2018-03-01

    In addition to the iconic wild species, such as the pandas and Siberian tigers, an ever-increasing number of domestic species are also threatened with extinction. Biobanking of spermatozoa could preserve genetic heritages of extinct species, and maintain biodiversity of existing species. Because lyophilized spermatozoa retain fertilizing capacity, the aim was to assess whether freeze-dried spermatozoa are an alternative option to save endangered sheep breeds. To achieve this objective, semen was collected from an Italian endangered sheep breed (Pagliarola), and a biobank of cryopreserved and freeze-dried spermatozoa was established, and evaluated using IVF (for frozen spermatozoa) and ICSI procedures (for frozen and freeze-dried spermatozoa). As expected, the fertilizing capacity of cryopreserved Pagliarola's spermatozoa was comparable to commercial semen stocks. To evaluate the activating capability of freeze-dried spermatozoa, 108 MII sheep oocytes were subjected to ICSI, and allocated to two groups: 56 oocytes were activated by incubation with ionomycin (ICSI-FDSa) and 52 were not activated (ICSI-FDSna). Pronuclear formation (2PN) was investigated at 14-16 h after ICSI in fixed presumptive zygotes. Only artificially activated oocytes developed into blastocysts after ICSI. In the present study, freeze-dried ram spermatozoa induced blastocyst development following ICSI at a relatively high proportion, providing evidence that sperm lyophilization is an alternative, low cost storage option for biodiversity preservation of domestic species. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effect of Freeze-Drying on the Antioxidant Compounds and Antioxidant Activity of Selected Tropical Fruits

    PubMed Central

    Shofian, Norshahida Mohamad; Hamid, Azizah Abdul; Osman, Azizah; Saari, Nazamid; Anwar, Farooq; Dek, Mohd Sabri Pak; Hairuddin, Muhammad Redzuan

    2011-01-01

    The effects of freeze-drying on antioxidant compounds and antioxidant activity of five tropical fruits, namely starfruit (Averrhoa carambola L.), mango (Mangifera indica L.), papaya (Carica papaya L.), muskmelon (Cucumis melo L.), and watermelon Citruluss lanatus (Thunb.) were investigated. Significant (p < 0.05) differences, for the amounts of total phenolic compounds (TPC), were found between the fresh and freeze-dried fruit samples, except muskmelon. There was no significant (p > 0.05) change, however, observed in the ascorbic acid content of the fresh and freeze-dried fruits. Similarly, freeze-drying did not exert any considerable effect on β-carotene concentration of fruits, except for mango and watermelon, where significantly (p < 0.05) higher levels were detected in the fresh samples. The results of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and reducing power assays revealed that fresh samples of starfruit and mango had relatively higher antioxidant activity. In case of linoleic acid peroxidation inhibition measurement, a significant (p < 0.05) but random variation was recorded between the fresh and freeze-dried fruits. Overall, in comparison to β-carotene and ascorbic acid, a good correlation was established between the result of TPC and antioxidant assays, indicating that phenolics might have been the dominant compounds contributing towards the antioxidant activity of the fruits tested. PMID:21845104

  15. Effect of freeze-drying on the antioxidant compounds and antioxidant activity of selected tropical fruits.

    PubMed

    Shofian, Norshahida Mohamad; Hamid, Azizah Abdul; Osman, Azizah; Saari, Nazamid; Anwar, Farooq; Dek, Mohd Sabri Pak; Hairuddin, Muhammad Redzuan

    2011-01-01

    The effects of freeze-drying on antioxidant compounds and antioxidant activity of five tropical fruits, namely starfruit (Averrhoa carambola L.), mango (Mangifera indica L.), papaya (Carica papaya L.), muskmelon (Cucumis melo L.), and watermelon Citruluss lanatus (Thunb.) were investigated. Significant (p < 0.05) differences, for the amounts of total phenolic compounds (TPC), were found between the fresh and freeze-dried fruit samples, except muskmelon. There was no significant (p > 0.05) change, however, observed in the ascorbic acid content of the fresh and freeze-dried fruits. Similarly, freeze-drying did not exert any considerable effect on β-carotene concentration of fruits, except for mango and watermelon, where significantly (p < 0.05) higher levels were detected in the fresh samples. The results of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and reducing power assays revealed that fresh samples of starfruit and mango had relatively higher antioxidant activity. In case of linoleic acid peroxidation inhibition measurement, a significant (p < 0.05) but random variation was recorded between the fresh and freeze-dried fruits. Overall, in comparison to β-carotene and ascorbic acid, a good correlation was established between the result of TPC and antioxidant assays, indicating that phenolics might have been the dominant compounds contributing towards the antioxidant activity of the fruits tested.

  16. Drying kinetics and characteristics of combined infrared-vacuum drying of button mushroom slices

    NASA Astrophysics Data System (ADS)

    Salehi, Fakhreddin; Kashaninejad, Mahdi; Jafarianlari, Ali

    2017-05-01

    Infrared-vacuum drying characteristics of button mushroom ( Agaricus bisporus) were evaluated in a combined dryer system. The effects of drying parameters, including infrared radiation power (150-375 W), system pressure (5-15 kPa) and time (0-160 min) on the drying kinetics and characteristics of button mushroom slices were investigated. Both the infrared lamp power and vacuum pressure influenced the drying time of button mushroom slices. The rate constants of the nine different kinetic's models for thin layer drying were established by nonlinear regression analysis of the experimental data which were found to be affected mainly by the infrared power level while system pressure had a little effect on the moisture ratios. The regression results showed that the Page model satisfactorily described the drying behavior of button mushroom slices with highest R value and lowest SE values. The effective moisture diffusivity increases as power increases and range between 0.83 and 2.33 × 10-9 m2/s. The rise in infrared power has a negative effect on the ΔE and with increasing in infrared radiation power it was increased.

  17. A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions.

    PubMed

    Dontireddy, Rakesh; Crean, Abina M

    2011-10-01

    Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.

  18. Freeze-drying of nanosuspensions, 1: freezing rate versus formulation design as critical factors to preserve the original particle size distribution.

    PubMed

    Beirowski, Jakob; Inghelbrecht, Sabine; Arien, Albertina; Gieseler, Henning

    2011-05-01

    It has been recently reported in the literature that using a fast freezing rate during freeze-drying of drug nanosuspensions is beneficial to preserve the original particle size distribution. All freezing rates studied were obtained by utilizing a custom-made apparatus and were then indirectly related to conventional vial freeze-drying. However, a standard freeze-dryer is only capable of achieving moderate freezing rates in the shelf fluid circulation system. Therefore, it was the purpose of the present study to evaluate the possibility to establish a typical freezing protocol applicable to a standard freeze-drying unit in combination with an adequate choice of cryoprotective excipients and steric stabilizers to preserve the original particle size distribution. Six different drug nanosuspensions containing itraconazole as a drug model were studied using freeze-thaw experiments and a full factorial design to reveal major factors for the stabilization of drug nanosuspensions and the corresponding interactions. In contrast to previous reports, the freezing regime showed no significant influence on preserving the original particle size distribution, suggesting that the concentrations of both the steric stabilizer and the cryoprotective agent are optimized. Moreover, it could be pinpointed that the combined effect of steric stabilizer and cryoprotectant clearly contribute to nanoparticle stability. Copyright © 2010 Wiley-Liss, Inc.

  19. Heat transfer characteristics of current primary packaging systems for pharmaceutical freeze-drying.

    PubMed

    Hibler, Susanne; Gieseler, Henning

    2012-11-01

    In the field of freeze-drying, the primary packaging material plays an essential role. Here, the packaging system not only contains and protects the drug product during storage and shipping, but it is also directly involved in the freeze-drying process itself. The heat transfer characteristics of the actual container system influence product temperature and therefore product homogeneity and quality as well as process performance. Consequently, knowledge of the container heat transfer characteristics is of vital importance for process optimization. It is the objective of this review article to provide a summary of research focused on heat transfer characteristics of different container systems for pharmaceutical freeze-drying. Besides the common tubing and molded glass vials and metal trays, more recent packaging solutions like polymer vials, LYOGUARD® trays, syringes, and blister packs are discussed. Recent developments in vial manufacturing are also taken into account. Copyright © 2012 Wiley Periodicals, Inc.

  20. Production of freeze-dried yeast culture for the brewing of traditional sorghum beer, tchapalo.

    PubMed

    N'Guessan, Florent K; Coulibaly, Hermann W; Alloue-Boraud, Mireille W A; Cot, Marlène; Djè, Koffi Marcellin

    2016-01-01

    Freeze-drying is a well-known dehydration method widely used to preserve microorganisms. In order to produce freeze-dried yeast starter culture for the brewing purpose of African sorghum beer, we tested protective agents (sucrose, glucose, glycerol) in combination with support materials (millet, maize, sorghum, and cassava flours) at 1:1 ratio (v/v). The yeast strains Saccharomyces cerevisiae F 12-7 and Candida tropicalis C 0-7 previously isolated from sorghum beer were used in a mixed culture at a ratio of 2:1 (C. tropicalis/S. cerevisiae). After the freeze-drying, the residual water contents were between 0.78 -2.27%, 0.55 -4.09%, and 0.40-2.61%, respectively, with sucrose, glucose and glycerol. The dried yeasts viabilities were between 4.0% and 10.6%. Among the protective agents used, sucrose was found to be the best protectant giving cell viabilities of 8.4-10.6%. Considering the support materials, millet flour was the best support after drying. When the freeze-dried yeast powders were stored at 4°C and room temperature (25-28°C) for up to 3 months, the survival rates were the highest with cassava flour as the support material.

  1. A novel dehydration technique for carrot slices implementing ultrasound and vacuum drying methods.

    PubMed

    Chen, Zhi-Gang; Guo, Xiao-Yu; Wu, Tao

    2016-05-01

    A novel drying technique using a combination of ultrasound and vacuum dehydration was developed to shorten the drying time and improve the quality of carrot slices. Carrot slices were dried with ultrasonic vacuum (USV) drying and vacuum drying at 65 °C and 75 °C. The drying rate was significantly influenced by the drying techniques and temperatures. Compared with vacuum drying, USV drying resulted in a 41-53% decrease in the drying time. The drying time for the USV and vacuum drying techniques at 75 °C was determined to be 140 and 340 min for carrot slices, respectively. The rehydration potential, nutritional value (retention of β-carotene and ascorbic acid), color, and textural properties of USV-dried carrot slices are predominately better compared to vacuum-dried carrot slices. Moreover, lower energy consumption was used in the USV technique. The drying data (time versus moisture ratio) were successfully fitted to Wang and Singh model. Copyright © 2015. Published by Elsevier B.V.

  2. Improving survival and storage stability of bacteria recalcitrant to freeze-drying: a coordinated study by European culture collections.

    PubMed

    Peiren, Jindrich; Buyse, Joke; De Vos, Paul; Lang, Elke; Clermont, Dominique; Hamon, Sylviane; Bégaud, Evelyne; Bizet, Chantal; Pascual, Javier; Ruvira, María A; Macián, M Carmen; Arahal, David R

    2015-04-01

    The objective of this study is to improve the viability after freeze-drying and during storage of delicate or recalcitrant strains safeguarded at biological resource centers. To achieve this objective, a joint experimental strategy was established among the different involved partner collections of the EMbaRC project ( www.embarc.eu ). Five bacterial strains considered as recalcitrant to freeze-drying were subjected to a standardized freeze-drying protocol and to seven agreed protocol variants. Viability of these strains was determined before and after freeze-drying (within 1 week, after 6 and 12 months, and after accelerated storage) for each of the protocols. Furthermore, strains were exchanged between partners to perform experiments with different freeze-dryer-dependent parameters. Of all tested variables, choice of the lyoprotectant had the biggest impact on viability after freeze-drying and during storage. For nearly all tested strains, skim milk as lyoprotectant resulted in lowest viability after freeze-drying and storage. On the other hand, best freeze-drying and storage conditions were strain and device dependent. For Aeromonas salmonicida CECT 894(T), best survival was obtained when horse serum supplemented with trehalose was used as lyoprotectant, while Aliivibrio fischeri LMG 4414(T) should be freeze-dried in skim milk supplemented with marine broth in a 1:1 ratio. Freeze-drying Campylobacter fetus CIP 53.96(T) using skim milk supplemented with trehalose as lyoprotectant resulted in best recovery. Xanthomonas fragariae DSM 3587(T) expressed high viability after freeze-drying and storage for all tested lyoprotectants and could not be considered as recalcitrant. In contrary, Flavobacterium columnare LMG 10406(T) did not survive the freeze-drying process under all tested conditions.

  3. Vacuum drying of apples (cv. Golden Delicious): drying characteristics, thermodynamic properties, and mass transfer parameters

    NASA Astrophysics Data System (ADS)

    Nadi, Fatemeh; Tzempelikos, Dimitrios

    2018-01-01

    In this work, apples of cv. Golden Delicious were cut into slices that were 5 and 7 mm thick and then vacuum dried at 50, 60 and 70 °C and pressure of 0.02 bar. The thin layer model drying kinetics was studied, and mass transfer properties, specifically effective moisture diffusivity and convective mass transfer coefficient, were evaluated using the Fick's equation of diffusion. Also, thermodynamic parameters of the process, i.e. enthalpy (ΔH), entropy (ΔS) and Gibbs free energy (ΔG), were determined. Colour properties were evaluated as one of the important indicators of food quality and marketability. Determination of mass transfer parameters and thermodynamic properties of vacuum dried apple slices has not been discussed much in the literature. In conclusion, the Nadi's model fitted best the observed data that represent the drying process. Thermodynamic properties were determined based on the dependence of the drying constant of the Henderson and Pabis model on temperature, and it was concluded that the variation in drying kinetics depends on the energy contribution of the surrounding environment. The enthalpy and entropy diminished, while the Gibbs free energy increased with the increase of the temperature of drying; therefore, it was possible to verify that variation in the diffusion process in the apple during drying depends on energetic contributions of the environment. The obtained results showed that diffusivity increased for 69%, while the mass transfer coefficient increase was even higher, 75%, at the variation of temperature of 20 °C. The increase in the dimensionless Biot number was 20%.

  4. Vacuum drying of apples (cv. Golden Delicious): drying characteristics, thermodynamic properties, and mass transfer parameters

    NASA Astrophysics Data System (ADS)

    Nadi, Fatemeh; Tzempelikos, Dimitrios

    2018-07-01

    In this work, apples of cv. Golden Delicious were cut into slices that were 5 and 7 mm thick and then vacuum dried at 50, 60 and 70 °C and pressure of 0.02 bar. The thin layer model drying kinetics was studied, and mass transfer properties, specifically effective moisture diffusivity and convective mass transfer coefficient, were evaluated using the Fick's equation of diffusion. Also, thermodynamic parameters of the process, i.e. enthalpy ( ΔH), entropy ( ΔS) and Gibbs free energy ( ΔG), were determined. Colour properties were evaluated as one of the important indicators of food quality and marketability. Determination of mass transfer parameters and thermodynamic properties of vacuum dried apple slices has not been discussed much in the literature. In conclusion, the Nadi's model fitted best the observed data that represent the drying process. Thermodynamic properties were determined based on the dependence of the drying constant of the Henderson and Pabis model on temperature, and it was concluded that the variation in drying kinetics depends on the energy contribution of the surrounding environment. The enthalpy and entropy diminished, while the Gibbs free energy increased with the increase of the temperature of drying; therefore, it was possible to verify that variation in the diffusion process in the apple during drying depends on energetic contributions of the environment. The obtained results showed that diffusivity increased for 69%, while the mass transfer coefficient increase was even higher, 75%, at the variation of temperature of 20 °C. The increase in the dimensionless Biot number was 20%.

  5. Mechanistic modelling of infrared mediated energy transfer during the primary drying step of a continuous freeze-drying process.

    PubMed

    Van Bockstal, Pieter-Jan; Mortier, Séverine Thérèse F C; De Meyer, Laurens; Corver, Jos; Vervaet, Chris; Nopens, Ingmar; De Beer, Thomas

    2017-05-01

    Conventional pharmaceutical freeze-drying is an inefficient and expensive batch-wise process, associated with several disadvantages leading to an uncontrolled end product variability. The proposed continuous alternative, based on spinning the vials during freezing and on optimal energy supply during drying, strongly increases process efficiency and improves product quality (uniformity). The heat transfer during continuous drying of the spin frozen vials is provided via non-contact infrared (IR) radiation. The energy transfer to the spin frozen vials should be optimised to maximise the drying efficiency while avoiding cake collapse. Therefore, a mechanistic model was developed which allows computing the optimal, dynamic IR heater temperature in function of the primary drying progress and which, hence, also allows predicting the primary drying endpoint based on the applied dynamic IR heater temperature. The model was validated by drying spin frozen vials containing the model formulation (3.9mL in 10R vials) according to the computed IR heater temperature profile. In total, 6 validation experiments were conducted. The primary drying endpoint was experimentally determined via in-line near-infrared (NIR) spectroscopy and compared with the endpoint predicted by the model (50min). The mean ratio of the experimental drying time to the predicted value was 0.91, indicating a good agreement between the model predictions and the experimental data. The end product had an elegant product appearance (visual inspection) and an acceptable residual moisture content (Karl Fischer). Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Drying behaviour, effective diffusivity and energy of activation of olive leaves dried by microwave, vacuum and oven drying methods

    NASA Astrophysics Data System (ADS)

    Elhussein, Elaf Abdelillah Ali; Şahin, Selin

    2018-07-01

    Drying is the crucial food processing for bioactive components from plant materials before strating extraction in addition to preservation of raw plant materials during storage period. Olive leaves were dried by various methods such as microwave drying (MD), oven drying (OD) and vacuum drying (VD) at several temperature values in the present study. Mathematical models allow to develop, design and control the processes. 14 emprical equations were used to estimate the drying behaviour and the time required for drying. Convenience of the models were evaluated according to the correlation coefficient ( R 2 ), varience ( S 2 ) and root mean square deviation ( D RMS ). On the other hand, the effective diffusion coefficient and energy for activation were also calculated. Effects of the drying methods on the total phenolic (TPC), flavonoid (TFC) and oleuropein contents and free radical scavenging activity (FRSA) of the olive leaves were also investigated to take into considiration the quality of the dried product. MD has proved to be the fastest drying method having the highest effective diffusivity and the lowest activation energy with a more qualitive product.

  7. Drying behaviour, effective diffusivity and energy of activation of olive leaves dried by microwave, vacuum and oven drying methods

    NASA Astrophysics Data System (ADS)

    Elhussein, Elaf Abdelillah Ali; Şahin, Selin

    2018-01-01

    Drying is the crucial food processing for bioactive components from plant materials before strating extraction in addition to preservation of raw plant materials during storage period. Olive leaves were dried by various methods such as microwave drying (MD), oven drying (OD) and vacuum drying (VD) at several temperature values in the present study. Mathematical models allow to develop, design and control the processes. 14 emprical equations were used to estimate the drying behaviour and the time required for drying. Convenience of the models were evaluated according to the correlation coefficient (R 2 ), varience (S 2 ) and root mean square deviation (D RMS ). On the other hand, the effective diffusion coefficient and energy for activation were also calculated. Effects of the drying methods on the total phenolic (TPC), flavonoid (TFC) and oleuropein contents and free radical scavenging activity (FRSA) of the olive leaves were also investigated to take into considiration the quality of the dried product. MD has proved to be the fastest drying method having the highest effective diffusivity and the lowest activation energy with a more qualitive product.

  8. Freeze drying for morphological control of inter-penetrating polymer networks

    NASA Technical Reports Server (NTRS)

    Hansen, Marion G.; Pater, Ruth H.

    1990-01-01

    The intrinsic brittleness of BMI resins can be reduced through the creation of an interpenetrating network (IPN) of BMI with a reactive-encapped thermoplastic, such as the presently considered polyimidesulfone, PISO2. The PISO2 and BMI were dissolved in a common solvent, which was then removed from the constituents by freeze drying; in an alternative method, an IPN was formed through dissolution of the constituent in a common solvent with either high or low melting point, followed by evaporative removal of the solvent. The effectiveness of the freeze-drying approach for morphological control is evaluated.

  9. Freeze drying for gas chromatography stationary phase deposition

    DOEpatents

    Sylwester, Alan P [Livermore, CA

    2007-01-02

    The present disclosure relates to methods for deposition of gas chromatography (GC) stationary phases into chromatography columns, for example gas chromatography columns. A chromatographic medium is dissolved or suspended in a solvent to form a composition. The composition may be inserted into a chromatographic column. Alternatively, portions of the chromatographic column may be exposed or filled with the composition. The composition is permitted to solidify, and at least a portion of the solvent is removed by vacuum sublimation.

  10. Freeze-Dried Carbon Nanotube Aerogels for High-Frequency Absorber Applications.

    PubMed

    Anoshkin, Ilya V; Campion, James; Lioubtchenko, Dmitri V; Oberhammer, Joachim

    2018-06-13

    A novel technique for millimeter wave absorber material embedded in a metal waveguide is proposed. The absorber material is a highly porous carbon nanotube (CNT) aerogel prepared by a freeze-drying technique. CNT aerogel structures are shown to be good absorbers with a low reflection coefficient, less than -12 dB at 95 GHz. The reflection coefficient of the novel absorber is 3-4 times lower than that of commercial absorbers with identical geometry. Samples prepared by freeze-drying at -25 °C demonstrate resonance behavior, while those prepared at liquid nitrogen temperature (-196 °C) exhibit a significant decrease in reflection coefficient, with no resonant behavior. CNT absorbers of identical volume based on wet-phase drying preparation show significantly worse performance than the CNT aerogel absorbers prepared by freeze-drying. Treatment of the freeze-dried CNT aerogel with n- and p-dopants (monoethanolamine and iodine vapors, respectively) shows remarkable improvement in the performance of the waveguide embedded absorbers, reducing the reflection coefficient by 2 dB across the band.

  11. Effect of the aerated structure on selected properties of freeze-dried hydrocolloid gels

    NASA Astrophysics Data System (ADS)

    Ciurzyńska, Agnieszka; Lenart, Andrzej

    2016-01-01

    The ability to create diverse structures and studies on the effect of the aerated structure on selected properties with the use of freeze-dried gels may provide knowledge about the properties of dried foods. Such gels can be a basis for obtaining innovative food products. For the gel preparation, 3 types of hydrocolloids were used: low-methoxyl pectin, a mixture of xanthan gum and locust-bean gum, and a mixture of xanthan gum and guar gum. Gels were aerated for 3 and 7 min, frozen at a temperature of -45°C 2 h-1, and freeze-dried at a temperature of 30°C. For the samples obtained, structure, porosity, shrinkage, rehydration, and colour were investigated. It was shown that the type of the hydrocolloid and aeration time influence the structure of freeze-dried gels, which determines such properties of samples as porosity, shrinkage, density, rehydration, and colour. The bigger pores of low-methoxyl pectin gels undergo rehydration in the highest degree. The delicate and aerated structure of gels with the mixture of xanthan gum and locust-bean gum was damaged during freeze-drying and shrinkage exhibited the highest value. Small pores of samples with the mixture of xanthan gum and guar gum were responsible for the lower rehydration properties, but the highest porosity value contributed to the highest lightness value.

  12. Development of freeze-dried albumin-free formulation of recombinant factor VIII SQ.

    PubMed

    Osterberg, T; Fatouros, A; Mikaelsson, M

    1997-07-01

    To develop a stable freeze-dried formulation of recombinant factor VIII-SQ (r-VIII SQ) without the addition of albumin. Different formulations were evaluated for their protective effect during sterile filtration, freeze-thawing, freeze-drying, reconstitution and long term storage. Factor VIII activity (VIII:C), visual inspection, clarity, solubility, moisture content and soluble aggregates and/ or fragments were assayed. A combination of non-crystallising excipients (L-histidine and sucrose), a non-ionic surfactant (polysorbate 80) and a crystalline bulking agent (sodium chloride) was found to preserve the factor VIII activity during formulation, freeze-drying and storage. Calcium chloride was included to prevent dissociation of the heavy and light chains of r-VIII SQ. Sodium chloride was chosen as the primary bulking agent since the concentration of sodium chloride necessary for dissolution of r-VIII SQ in the buffer will inhibit the crystallization of many potential cake formers. It was found that L-histidine, besides functioning as a buffer, also protected r-VIII SQ during freeze-drying and storage. A pH close to 7 was found to be optimal. Some potential macromolecular stabilisers, PEG 4000, Haes-steril and Haemaccel, were evaluated but they did not improve the recovery of VIII:C. The freeze-dried formulation was stable for at least two years at 7 degrees C and for at least one year at 25 degrees C. The reconstituted solution was stable for at least 100 hours at 25 degrees C. The albumin-free formulation resulted in consistently high recovery of VIII:C, very low aggregate formation and good storage stability. The stability of the reconstituted solution makes the formulation suitable for continuous administration via infusion pump. The formulation strategy described here may also be useful for other proteins which require a high ionic strength.

  13. Use of a soft sensor for the fast estimation of dried cake resistance during a freeze-drying cycle.

    PubMed

    Bosca, Serena; Barresi, Antonello A; Fissore, Davide

    2013-07-15

    This paper deals with the determination of dried cake resistance in a freeze-drying process using the Smart Soft Sensor, a process analytical technology recently proposed by the authors to monitor the primary drying stage of a freeze-drying process. This sensor uses the measurement of product temperature, a mathematical model of the process, and the Kalman filter algorithm to estimate the residual amount of ice in the vial as a function of time, as well as the coefficient of heat transfer between the shelf and the product and the resistance of the dried cake to vapor flow. It does not require expensive (additional) hardware in a freeze-dryer, provided that thermocouples are available. At first, the effect of the insertion of the thermocouple in a vial on the structure of the product is investigated by means of experimental tests, comparing both sublimation rate and cake structure in vials with and without thermocouple. This is required to assess that the temperature measured by the thermocouple is the same of the product in the non-monitored vials, at least in a non-GMP environment, or when controlled nucleation methods are used. Then, results about cake resistance obtained in an extended experimental campaign with aqueous solutions containing different excipients (sucrose, mannitol and polyvinylpyrrolidone), processed in various operating conditions, are presented, with the goal to point out the accuracy of the proposed methodology. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Microencapsulation by freeze-drying of potassium norbixinate and curcumin with maltodextrin: stability, solubility, and food application.

    PubMed

    Sousdaleff, Mirian; Baesso, Mauro Luciano; Medina Neto, Antonio; Nogueira, Ana Cláudia; Marcolino, Vanessa Aparecida; Matioli, Graciette

    2013-01-30

    Stability of potassium norbixinate and curcumin by microencapsulation with maltodextrin DE20 and freeze-drying was evaluated as a function of exposition to light, air, different pH, water solubility, and in food applications. The best results were obtained with microencapsulated potassium norbixinate 1:20, which, when vacuum-packed and in the presence of natural light, showed color retention of 78%, while microencapsulated curcumin 1:20 showed color retention of 71%. Differential scanning calorimetry and thermogravimetry provided an indication of interaction between colorants and maltodextrin. Photoacoustic spectroscopy (PAS) showed that free and microencapsulated colorants exhibited high rates of absorption throughout the measured spectral region. This work evidenced that the freeze-drying process is favorable for microencapsulation of curcumin by maltodextrin, providing improved solubility to the microencapsulated colorant. Both microencapsulated colorants showed relevant results for use in a wide range of pH and food applications. The PAS technique was useful for the evaluation of the stability of free and microencapsulated colorants.

  15. Effects of buffer composition and processing conditions on aggregation of bovine IgG during freeze-drying.

    PubMed

    Sarciaux, J M; Mansour, S; Hageman, M J; Nail, S L

    1999-12-01

    The objective of this study was to identify critical formulation and processing variables affecting aggregation of bovine IgG during freeze-drying when no lyoprotective solute is used. Parameters examined were phosphate buffer concentration and counterion (Na versus K phosphate), added salts, cooling rate, IgG concentration, residual moisture level, and presence of a surfactant. No soluble aggregates were detected in any formulation after either freezing/thawing or freeze-drying. No insoluble aggregates were detected in any formulation after freezing, but insoluble aggregate levels were always detectable after freeze-drying. The data are consistent with a mechanism of aggregate formation involving denaturation of IgG at the ice/freeze-concentrate interface which is reversible upon freeze-thawing, but becomes irreversible after freeze-drying and reconstitution. Rapid cooling (by quenching in liquid nitrogen) results in more and larger aggregates than slow cooling on the shelf of the freeze-dryer. This observation is consistent with surface area measurements and environmental electron microscopic data showing a higher surface area of freeze-dried solids after fast cooling. Annealing of rapidly cooled solutions results in significantly less aggregation in reconstituted freeze-dried solids than in nonannealed controls, with a corresponding decrease in specific surface area of the freeze-dried, annealed system. Increasing the concentration of IgG significantly improves the stability of IgG against freeze-drying-induced aggregation, which may be explained by a smaller percentage of the protein residing at the ice/freeze-concentrate interface as IgG concentration is increased. A sodium phosphate buffer system consistently results in more turbid reconstituted solids than a potassium phosphate buffer system at the same concentration, but this effect is not attributable to a pH shift during freezing. Added salts such as NaCl or KCl contribute markedly to insoluble aggregate

  16. Electronic Nose Characterization of the Quality Parameters of Freeze-Dried Bacteria

    NASA Astrophysics Data System (ADS)

    Capuano, R.; Santonico, M.; Martinelli, E.; Paolesse, R.; Passot, S.; Fonseca, F.; Cenard, S.; Trelea, C.; Di Natale, C.

    2011-09-01

    Freeze-drying is the method of choice for preserving heat sensitive biological products such as microorganisms. The development of a fast analytical method for evaluating the properties of the dehydrated bacteria is then necessary for a proper utilization of the product in several food processes. In this paper, dried bacteria headspace is analyzed by a GC-MS and an electronic nose. Results indicate that headspace contains enough information to assess the products quality.

  17. Optimization of freeze drying conditions for purified pectinase from mango (Mangifera indica cv. Chokanan) peel.

    PubMed

    Mehrnoush, Amid; Mustafa, Shuhaimi; Yazid, Abdul Manap Mohd

    2012-01-01

    Response surface methodology (RSM) along with central composite design (CCD) was applied to optimize the freeze drying conditions for purified pectinase from mango (Mangifera indica cv. Chokanan) peel. The effect of pectinase content (-2.66, 62.66 mg/mL), Arabic gum (-1.21, 10.21%, w/v), and maltodextrin (0.73, 7.26%, w/v) as independent variables on activity, yield, and storage stability of freeze-dried enzyme was evaluated. Storage stability of pectinase was investigated after one week at 4 °C and yield percentage of the enzyme after encapsulation was also determined. The independent variables had the most significant (p < 0.05) effect on pectinase activity and yield of the enzyme. It was observed that the interaction effect of Arabic gum and maltodextrin improved the enzymatic properties of freeze-dried pectinase. The optimal conditions for freeze-dried pectinase from mango peel were obtained using 30 mg/mL of pectinase content, 4.5 (%, w/v) of Arabic gum, and 4 (%, w/v) of maltodextrin. Under these conditions, the maximum activity (11.12 U/mL), yield (86.4%) and storage stability (84.2%) of encapsulated pectinase were achieved.

  18. Optimization of Freeze Drying Conditions for Purified Pectinase from Mango (Mangifera indica cv. Chokanan) Peel

    PubMed Central

    Mehrnoush, Amid; Mustafa, Shuhaimi; Yazid, Abdul Manap Mohd

    2012-01-01

    Response surface methodology (RSM) along with central composite design (CCD) was applied to optimize the freeze drying conditions for purified pectinase from mango (Mangifera indica cv. Chokanan) peel. The effect of pectinase content (−2.66, 62.66 mg/mL), Arabic gum (−1.21, 10.21%, w/v), and maltodextrin (0.73, 7.26%, w/v) as independent variables on activity, yield, and storage stability of freeze-dried enzyme was evaluated. Storage stability of pectinase was investigated after one week at 4 °C and yield percentage of the enzyme after encapsulation was also determined. The independent variables had the most significant (p < 0.05) effect on pectinase activity and yield of the enzyme. It was observed that the interaction effect of Arabic gum and maltodextrin improved the enzymatic properties of freeze-dried pectinase. The optimal conditions for freeze-dried pectinase from mango peel were obtained using 30 mg/mL of pectinase content, 4.5 (%, w/v) of Arabic gum, and 4 (%, w/v) of maltodextrin. Under these conditions, the maximum activity (11.12 U/mL), yield (86.4%) and storage stability (84.2%) of encapsulated pectinase were achieved. PMID:22489134

  19. [Optimization of lyophilization procedures for freeze-drying of human red blood cells].

    PubMed

    Chen, Lin-feng; Liu, Jing-han; Wang, De-qing; Ouyang, Xi-lin; Zhuang, Yuan; Che, Ji; Yu, Yang; Li, Hui

    2010-09-01

    To investigate the different parameters of the lyophilization procedures that affect the recovery of the rehydrated red blood cells (RBCs). Human RBCs loaded in tubes were cooled with 4 different modes and subjected to water bath at 25 degrees celsius;. The morphological changes of the RBCs were observed to assess the degree of vitrification, and the specimens were placed in the freeze-dryer with the temperature set up at 40, -50, -60, -70 and -80 degrees celsius;. The rates of temperature rise of the main and secondary drying in the lyophilization procedures were compared, and the water residue in the specimens was determined. The protectant did not show ice crystal in the course of freezing and thawing. No significant difference was found in the recovery rate of the rehydrated RBCs freeze-dried at the minimum temperature of -70 degrees celsius; and -80 degrees celsius; (P > 0.05). The E procedure resulted in the maximum recovery of the RBCs (83.14% ± 9.55%) and Hb (85.33% ± 11.42%), showing significant differences from the other groups(P < 0.01 or 0.05). The recovery of the RBCs showed a positive correlation to the water residue in the samples. Fast cooling in liquid nitrogen and shelf precooling at -70 degrees celsius; with a moderate rate of temperature rise in lyophylization and a start dry temperature close to the shelf equilibrium temperature produce optimal freeze-drying result of human RBCs.

  20. Effect of Carboxylmethyl Cellulose Coating and Osmotic Dehydration on Freeze Drying Kinetics of Apple Slices

    PubMed Central

    Rahimi, Jamshid; Singh, Ashutosh; Adewale, Peter Olusola; Adedeji, Akinbode A.; Ngadi, Michael O.; Raghavan, Vijaya

    2013-01-01

    The effect of different concentrations of sugar solution (hypertonic) (30%, 45% and 60% w/v) and carboxyl methyl cellulose (CMC) (0%, 1% and 2% w/v) coating on freeze drying of apple slices was studied. In total, nine treatments with respect to concentrations of hypertonic solution and coating layer were prepared to analyze their influence on the physical and chemical properties of freeze dried apple slices. It was observed that increase in the sugar solution concentration, decreased the moisture content of the apple slices significantly impacting its water activity, texture and sugar gain. Application of different concentrations of CMC coating had no significant effect on the properties of dried apple slices. A significant change was observed for color of CMC coated freeze dried apple slices pretreated with 60% sugar solution. Drying kinetics of pretreated apple slices were fitted by using two drying models, Newton’s and Page’s. Page’s model showed higher R-square and lower root mean square error (RSME) compared to Newton’s model. PMID:28239107

  1. Improving the Quality of Freeze Dried Rice: Initial Evaluations

    DTIC Science & Technology

    2015-05-01

    and 18–25 minutes, respectively). Rice starch leached out while boiling, thus the longer it was boiled, the paler and more transparent the rice...reproducible results, possibly through allowing the starch to become fully gelatinised resulting in better colour, flavour, texture as well as physical...less water and less time. Basmati Pleasant aroma and taste, good flavour, good texture with slight resistance on bite. Parboiled Dry on palate

  2. Stability of prothrombin and factor VII in freeze-dried plasma

    PubMed Central

    Brozović, M.; Gurd, L. J.; Robertson, I.; Bangham, D. R.

    1971-01-01

    The stability of prothrombin and factor VII was studied using accelerated degradation tests in three preparations of freeze-dried pooled normal plasmas. In a previous report (Brozović, Gurd, Robertson, and Bangham, 1971) factor X was shown to be relatively unstable in these preparations of freeze-dried plasma: it was calculated that up to 8% of the original factor X activity would be lost after 10 years at −20°C, up to 54% at 4°C, and up to 90% at room temperature. The losses of factor VII activity were estimated to be negligible at −20°C, between 2 and 18% at 4°C, and between 20 and 70% of the original activity at 20°C, after 10 years of storage. Prothrombin was found to be less stable than factor VII: the expected loss in 10 years at −20°C may be up to 4%, at 4°C up to 30%, and at 20°C up to 83% of the initial activity. These findings indicate that in freeze-dried plasma prothrombin as well as factor X may be insufficiently stable for plasma to serve as long-term reference material for the standardization of the one-stage prothrombin time. Moreover, the loss of prothrombin and factor X in freeze-dried plasma stored at 4°C may be so high that when it is required to preserve these factors it may be necessary to store freeze-dried plasma at lower temperatures. PMID:5130534

  3. Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During Freeze-Drying.

    PubMed

    Fang, Rui; Tanaka, Kazunari; Mudhivarthi, Vamsi; Bogner, Robin H; Pikal, Michael J

    2018-03-01

    Several controlled ice nucleation techniques have been developed to increase the efficiency of the freeze-drying process as well as to improve the quality of pharmaceutical products. Owing to the reduction in ice surface area, these techniques have the potential to reduce the degradation of proteins labile during freezing. The objective of this study was to evaluate the effect of ice nucleation temperature on the in-process stability of lactate dehydrogenase (LDH). LDH in potassium phosphate buffer was nucleated at -4°C, -8°C, and -12°C using ControLyo™ or allowed to nucleate spontaneously. Both the enzymatic activity and tetramer recovery after freeze-thawing linearly correlated with product ice nucleation temperature (n = 24). Controlled nucleation also significantly improved batch homogeneity as reflected by reduced inter-vial variation in activity and tetramer recovery. With the correlation established in the laboratory, the degradation of protein in manufacturing arising from ice nucleation temperature differences can be quantitatively predicted. The results show that controlled nucleation reduced the degradation of LDH during the freezing process, but this does not necessarily translate to vastly superior stability during the entire freeze-drying process. The capability of improving batch homogeneity provides potential advantages in scaling-up from lab to manufacturing scale. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Quality by design: optimization of a freeze-drying cycle via design space in case of heterogeneous drying behavior and influence of the freezing protocol.

    PubMed

    Pisano, Roberto; Fissore, Davide; Barresi, Antonello A; Brayard, Philippe; Chouvenc, Pierre; Woinet, Bertrand

    2013-02-01

    This paper shows how to optimize the primary drying phase, for both product quality and drying time, of a parenteral formulation via design space. A non-steady state model, parameterized with experimentally determined heat and mass transfer coefficients, is used to define the design space when the heat transfer coefficient varies with the position of the vial in the array. The calculations recognize both equipment and product constraints, and also take into account model parameter uncertainty. Examples are given of cycles designed for the same formulation, but varying the freezing conditions and the freeze-dryer scale. These are then compared in terms of drying time. Furthermore, the impact of inter-vial variability on design space, and therefore on the optimized cycle, is addressed. With this regard, a simplified method is presented for the cycle design, which reduces the experimental effort required for the system qualification. The use of mathematical modeling is demonstrated to be very effective not only for cycle development, but also for solving problem of process transfer. This study showed that inter-vial variability remains significant when vials are loaded on plastic trays, and how inter-vial variability can be taken into account during process design.

  5. Atmospheric Spray Freeze-Drying: Numerical Modeling and Comparison With Experimental Measurements.

    PubMed

    Borges Sebastião, Israel; Robinson, Thomas D; Alexeenko, Alina

    2017-01-01

    Atmospheric spray freeze-drying (ASFD) represents a novel approach to dry thermosensitive solutions via sublimation. Tests conducted with a second-generation ASFD equipment, developed for pharmaceutical applications, have focused initially on producing a light, fine, high-grade powder consistently and reliably. To better understand the heat and mass transfer physics and drying dynamics taking place within the ASFD chamber, 3 analytical models describing the key processes are developed and validated. First, by coupling the dynamics and heat transfer of single droplets sprayed into the chamber, the velocity, temperature, and phase change evolutions of these droplets are estimated for actual operational conditions. This model reveals that, under typical operational conditions, the sprayed droplets require less than 100 ms to freeze. Second, because understanding the heat transfer throughout the entire freeze-drying process is so important, a theoretical model is proposed to predict the time evolution of the chamber gas temperature. Finally, a drying model, calibrated with hygrometer measurements, is used to estimate the total time required to achieve a predefined final moisture content. Results from these models are compared with experimental data. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. Technological Development of Brewing in Domestic Refrigerator Using Freeze-Dried Raw Materials

    PubMed Central

    2017-01-01

    Summary Development of a novel directly marketable beer brewed at low temperature in a domestic refrigerator combined with yeast immobilization technology is presented in this study. Separately, freeze-dried wort and immobilized cells of the cryotolerant yeast strain Saccharomyces cerevisiae AXAZ-1 on tubular cellulose were used in low-temperature fermentation (2, 5 and 7 °C). The positive effect of tubular cellulose during low-temperature brewing was examined, revealing that freeze-dried immobilized yeast cells on tubular cellulose significantly reduced the fermentation rates in contrast to freeze-dried free cells, although they are recommended for home-made beer production. Immobilization also enhanced the yeast resistance at low-temperature fermentation, reducing the minimum brewing temperature value from 5 to 2 °C. In the case of high-quality beer production, the effect of temperature and initial sugar concentration on the fermentation kinetics were assessed. Sensory enrichment of the produced beer was confirmed by the analysis of the final products, revealing a low diacetyl concentration, together with improved polyphenol content, aroma profile and clarity. The proposed process for beer production in a domestic refrigerator can easily be commercialized and applied by dissolving the content of two separate packages in tap water; one package containing dried wort and the other dried immobilized cells on tubular cellulose suspended in tap water. PMID:29089847

  7. Technological Development of Brewing in Domestic Refrigerator Using Freeze-Dried Raw Materials.

    PubMed

    Gialleli, Angelika-Ioanna; Ganatsios, Vassilios; Terpou, Antonia; Kanellaki, Maria; Bekatorou, Argyro; Koutinas, Athanasios A; Dimitrellou, Dimitra

    2017-09-01

    Development of a novel directly marketable beer brewed at low temperature in a domestic refrigerator combined with yeast immobilization technology is presented in this study. Separately, freeze-dried wort and immobilized cells of the cryotolerant yeast strain Saccharomyces cerevisiae AXAZ-1 on tubular cellulose were used in low-temperature fermentation (2, 5 and 7 °C). The positive effect of tubular cellulose during low-temperature brewing was examined, revealing that freeze-dried immobilized yeast cells on tubular cellulose significantly reduced the fermentation rates in contrast to freeze-dried free cells, although they are recommended for home-made beer production. Immobilization also enhanced the yeast resistance at low-temperature fermentation, reducing the minimum brewing temperature value from 5 to 2 °C. In the case of high-quality beer production, the effect of temperature and initial sugar concentration on the fermentation kinetics were assessed. Sensory enrichment of the produced beer was confirmed by the analysis of the final products, revealing a low diacetyl concentration, together with improved polyphenol content, aroma profile and clarity. The proposed process for beer production in a domestic refrigerator can easily be commercialized and applied by dissolving the content of two separate packages in tap water; one package containing dried wort and the other dried immobilized cells on tubular cellulose suspended in tap water.

  8. Reduced pressure ice fog technique for controlled ice nucleation during freeze-drying.

    PubMed

    Patel, Sajal M; Bhugra, Chandan; Pikal, Michael J

    2009-01-01

    A method to achieve controlled ice nucleation during the freeze-drying process using an ice fog technique was demonstrated in an earlier report. However, the time required for nucleation was about 5 min, even though only one shelf was used, which resulted in Ostwald ripening (annealing) in some of the vials that nucleated earlier than the others. As a result, the ice structure was not optimally uniform in all the vials. The objective of the present study is to introduce a simple variation of the ice fog method whereby a reduced pressure in the chamber is utilized to allow more rapid and uniform freezing which is also potentially easier to scale up. Experiments were conducted on a lab scale freeze dryer with sucrose as model compound at different concentration, product load, and fill volume. Product resistance during primary drying was measured using manometric temperature measurement. Specific surface area of the freeze-dried cake was also determined. No difference was observed either in average product resistance or specific surface area for the different experimental conditions studied, indicating that with use of the reduced pressure ice fog technique, the solutions nucleated at very nearly the same temperature (-10 degrees C). The striking feature of the "Reduced Pressure Ice Fog Technique" is the rapid ice nucleation (less than a minute) under conditions where the earlier procedure required about 5 min; hence, effects of variable Ostwald ripening were not an issue.

  9. Development of a nanosuspension for iv administration: From miniscale screening to a freeze dried formulation.

    PubMed

    Frank, Kerstin J; Boeck, Georg

    2016-05-25

    The aim was to develop a nanosuspension of the poorly soluble BI XX. The nanosuspension is intended for intravenous (iv) administration in preclinical studies and should not cause any unwanted side effects. Thus, only stabilizers that are accepted for iv application should be used and isotonicity, euhydria and the absence of living microorganisms were targeted. Suspensions were prepared in a ball-mill (mixing mill MM 400 from Retsch). There were various vials used as containers; HPLC-vials were used for the small scale screening of stabilizers and injection vials for preparation of larger quantities of the nanosuspensions. Particle size distribution was analyzed by laser diffraction measurement (Mastersizer 2000). Lyophilization was used for processing of the suspensions (Christ freeze dryer). Stable nanosuspensions (d90 remained <1μm up to 7days) were prepared with several FDA-accepted stabilizers. Freeze drying was evaluated for one formulation containing 2% of the API, 0.5% of arginine and 4% of mannitol. The particle size distribution before freeze drying and after re-dispersion was comparable. After milling for 2h, no living microorganisms were detected in the nanosuspension. Various FDA accepted excipients were identified which resulted in stable nanosuspensions of BI XX. The most stable formulation was successfully freeze dried. It was proven that milling in the ball-mill decreases the presence of living microorganisms. Copyright © 2016. Published by Elsevier B.V.

  10. Mechanisms of deterioration of nutrients. [retention of flavor during freeze drying

    NASA Technical Reports Server (NTRS)

    Karel, M.; Flink, J. M.

    1975-01-01

    The retention of flavor during freeze drying was studied with model systems. Mechanisms by which flavor retention phenomena is explained were developed and process conditions specified so that flavor retention is optimized. The literature is reviewed and results of studies of the flavor retention behavior of a number of real food products, including both liquid and solid foods are evaluated. Process parameters predicted by the mechanisms to be of greatest significance are freezing rate, initial solids content, and conditions which result in maintenance of sample structure. Flavor quality for the real food showed the same behavior relative to process conditions as predicted by the mechanisms based on model system studies.

  11. In-line multipoint near-infrared spectroscopy for moisture content quantification during freeze-drying.

    PubMed

    Kauppinen, Ari; Toiviainen, Maunu; Korhonen, Ossi; Aaltonen, Jaakko; Järvinen, Kristiina; Paaso, Janne; Juuti, Mikko; Ketolainen, Jarkko

    2013-02-19

    During the past decade, near-infrared (NIR) spectroscopy has been applied for in-line moisture content quantification during a freeze-drying process. However, NIR has been used as a single-vial technique and thus is not representative of the entire batch. This has been considered as one of the main barriers for NIR spectroscopy becoming widely used in process analytical technology (PAT) for freeze-drying. Clearly it would be essential to monitor samples that reliably represent the whole batch. The present study evaluated multipoint NIR spectroscopy for in-line moisture content quantification during a freeze-drying process. Aqueous sucrose solutions were used as model formulations. NIR data was calibrated to predict the moisture content using partial least-squares (PLS) regression with Karl Fischer titration being used as a reference method. PLS calibrations resulted in root-mean-square error of prediction (RMSEP) values lower than 0.13%. Three noncontact, diffuse reflectance NIR probe heads were positioned on the freeze-dryer shelf to measure the moisture content in a noninvasive manner, through the side of the glass vials. The results showed that the detection of unequal sublimation rates within a freeze-dryer shelf was possible with the multipoint NIR system in use. Furthermore, in-line moisture content quantification was reliable especially toward the end of the process. These findings indicate that the use of multipoint NIR spectroscopy can achieve representative quantification of moisture content and hence a drying end point determination to a desired residual moisture level.

  12. Freeze-Drying of Plant Tissue Containing HBV Surface Antigen for the Oral Vaccine against Hepatitis B

    PubMed Central

    Milczarek, Magdalena; Pajtasz-Piasecka, Elżbieta; Wietrzyk, Joanna

    2014-01-01

    The aim of this study was to develop a freeze-drying protocol facilitating successful processing of plant material containing the small surface antigen of hepatitis B virus (S-HBsAg) while preserving its VLP structure and immunogenicity. Freeze-drying of the antigen in lettuce leaf tissue, without any isolation or purification step, was investigated. Each process step was consecutively evaluated and the best parameters were applied. Several drying profiles and excipients were tested. The profile of 20°C for 20 h for primary and 22°C for 2 h for secondary drying as well as sucrose expressed efficient stabilisation of S-HBsAg during freeze-drying. Freezing rate and postprocess residual moisture were also analysed as important factors affecting S-HBsAg preservation. The process was reproducible and provided a product with VLP content up to 200 µg/g DW. Assays for VLPs and total antigen together with animal immunisation trials confirmed preservation of antigenicity and immunogenicity of S-HBsAg in freeze-dried powder. Long-term stability tests revealed that the stored freeze-dried product was stable at 4°C for one year, but degraded at elevated temperatures. As a result, a basis for an efficient freeze-drying process has been established and a suitable semiproduct for oral plant-derived vaccine against HBV was obtained. PMID:25371900

  13. Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

    PubMed

    Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

    2015-12-30

    The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses.

    PubMed

    Van Bockstal, Pieter-Jan; De Meyer, Laurens; Corver, Jos; Vervaet, Chris; De Beer, Thomas

    2017-01-01

    Recently, an innovative continuous freeze-drying concept for unit doses was proposed, based on spinning the vials during freezing. An efficient heat transfer during drying is essential to continuously process these spin frozen vials. Therefore, the applicability of noncontact infrared (IR) radiation was examined. The impact of several process and formulation variables on the mass of sublimed ice after 15 min of primary drying (i.e., sublimation rate) and the total drying time was examined. Two experimental designs were performed in which electrical power to the IR heaters, distance between the IR heaters and the spin frozen vial, chamber pressure, product layer thickness, and 5 model formulations were included as factors. A near-infrared spectroscopy method was developed to determine the end point of primary and secondary drying. The sublimation rate was mainly influenced by the electrical power to the IR heaters and the distance between the IR heaters and the vial. The layer thickness had the largest effect on total drying time. The chamber pressure and the 5 model formulations had no significant impact on sublimation rate and total drying time, respectively. This study shows that IR radiation is suitable to provide the energy during the continuous processing of spin frozen vials. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Care during freeze-drying of bovine pericardium tissue to be used as a biomaterial: a comparative study.

    PubMed

    Polak, Roberta; Pitombo, Ronaldo N M

    2011-10-01

    Bovine pericardium (BP) tissue is widely used in the manufacture of bioprosthetics. The effects of freeze-drying on the BP tissue have been studied by some researchers in order to decrease their cytotoxicity due to preservation in formaldehyde solution, and to increase the lifetime of the product in storage. This study was undertaken in order to study the effect of freeze-drying in the structure of BP. To perform this study BP samples were freeze-dried in two different types of freeze-dryers available in our laboratory: a laboratory freeze-dryer, in which it was not possible to control parameters and a pilot freeze-dryer, wherein all parameters during freezing and drying were controlled. After freeze-drying processes, samples were analyzed by SEM, Raman spectroscopy, tensile strength, water uptake tests and TEM. In summary, it has been demonstrated that damages occur in collagen fibers by the loss of bulk water of collagen structure implicating in a drastic decreasing of BP mechanical properties due to its structural alterations. Moreover, it was proven that the collagen fibrils suffered breakage at some points, which can be attributed to the uncontrolled parameters during drying. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Stability Studies of a Freeze-Dried Recombinant Human Epidermal Growth Factor Formulation for Wound Healing.

    PubMed

    Santana, Héctor; García, Gerardo; Vega, Maribel; Beldarraín, Alejandro; Páez, Rolando

    2015-01-01

    We report on the stability assessment of a recombinant human epidermal growth factor (rhEGF) freeze-dried formulation for wound healing by intra-lesional injections. The suitability of packaging material for the light protection of finished dried powder was evaluated after stressed exposure conditions. Degradation kinetics of powder for injection was investigated at concentrations of 25-250 μg/vial and temperatures of 45, 60, and 70 °C. The long-term stability was evaluated after storage at 25 ± 2 °C/60 ± 5% relative humidity (6 months) and 2-8 °C (24 months) in the dark and analyzed at several time points. The stability after reconstitution with various diluents was also assessed after 24 h storage at 2-8 °C. The rhEGF samples were analyzed for structural integrity by reversed-phase high-performance liquid chromatography (RP-HPLC), size-exclusion HPLC, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Biological activity was investigated by measuring the cell proliferation in a murine fibroblast cell line. Results show that freeze-dried rhEGF in primary packaging only was photosensitive, as degradation by RP-HPLC that was completely suppressed by the secondary carton package was revealed. An increase in freeze-dried rhEGF stability was observed with the increase in protein concentration from 25 to 250 μg/vial. The long-term stability study showed no significant rhEGF degradation or physical change within the freeze-dried formulations containing 25 or 250 μg/vial of rhEGF. No physical, chemical or biological changes were observed for rhEGF after reconstitution in water for injection or 0.9% sodium chloride during the storage conditions studied. The stability of a recombinant human epidermal growth factor (rhEGF) freeze-dried formulation for wound healing by intra-lesional injections was assessed. The suitability of packaging material for the light protection of finished dried powder was evaluated after stressed exposure conditions

  17. Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation

    PubMed Central

    Flood, Alexander; Chen, Dexiang

    2016-01-01

    An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness. PMID:27851765

  18. Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation.

    PubMed

    Flood, Alexander; Estrada, Marcus; McAdams, David; Ji, Yuhua; Chen, Dexiang

    2016-01-01

    An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness.

  19. Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.

    PubMed

    Pozzoli, Michele; Traini, Daniela; Young, Paul M; Sukkar, Maria B; Sonvico, Fabio

    2017-09-01

    The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus ® (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route. The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus-BUD formulation. The freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334 ± 0.0178 m 2 /g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension. Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.

  20. The effect of variety and maturity on the quality of freeze-dried carrots. The effect of microwave blanching on the nutritional and textural quality of freeze-dried spinach

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Using carrots, the quality of freeze-dried products was studied to determine the optimum varieties and maturation stages for quality attributes such as appearance, flavor, texture, and nutritive value. The quality of freeze-dried carrots is discussed in terms of Gardner color, alcohol insoluble solids, viscosity, and core/cortex ratio. Also, microwave blanching of freeze-dried spinach was studied to determine vitamin interrelationships, anatomical changes, and oxidative deteriorations in terms of preprocessing microwave treatments. Statistical methods were employed in the gathering of data and interpretation of results in both studies.

  1. Effects of vial packing density on drying rate during freeze-drying of carbohydrates or a model protein measured using a vial-weighing technique.

    PubMed

    Gieseler, Henning; Lee, Geoffrey

    2008-02-01

    To determine the effects of vial packing density in a laboratory freeze dryer on drying rate profiles of crystalline and amorphous formulations. The Christ freeze-drying balance measured cumulative water loss, m(t), and instantaneous drying rate, m(t), of water, mannitol, sucrose and sucrose/BSA formulations in commercial vials. Crystalline mannitol shows drying rate behaviour indicative of a largely homogeneous dried-product layer. The drying rate behaviour of amorphous sucrose indicates structural heterogeneity, postulated to come from shrinkage or microcollapse. Trehalose dries more slowly than sucrose. Addition of BSA to either disaccharide decreases primary drying time. Higher vial packing density greatly reduces drying rate because of effects of radiation heat transfer from chamber walls to test vial. Plots of m(t) versus radical t and m(t) versus layer thickness (either ice or dried-product) allow interpretation of changes in internal cake morphology during drying. Vial packing density greatly influences these profiles.

  2. State transitions and physicochemical aspects of cryoprotection and stabilization in freeze-drying of Lactobacillus rhamnosus GG (LGG).

    PubMed

    Pehkonen, K S; Roos, Y H; Miao, S; Ross, R P; Stanton, C

    2008-06-01

    The frozen and dehydrated state transitions of lactose and trehalose were determined and studied as factors affecting the stability of probiotic bacteria to understand physicochemical aspects of protection against freezing and dehydration of probiotic cultures. Lactobacillus rhamnosus GG was frozen (-22 or -43 degrees C), freeze-dried and stored under controlled water vapour pressure (0%, 11%, 23% and 33% relative vapour pressure) conditions. Lactose, trehalose and their mixture (1 : 1) were used as protective media. These systems were confirmed to exhibit relatively similar state transition and water plasticization behaviour in freeze-concentrated and dehydrated states as determined by differential scanning calorimetry. Ice formation and dehydrated materials were studied using cold-stage microscopy and scanning electron microscopy. Trehalose and lactose-trehalose gave the most effective protection of cell viability as observed from colony forming units after freezing, dehydration and storage. Enhanced cell viability was observed when the freezing temperature was -43 degrees C. State transitions of protective media affect ice formation and cell viability in freeze-drying and storage. Formation of a maximally freeze-concentrated matrix with entrapped microbial cells is essential in freezing prior to freeze-drying. Freeze-drying must retain a solid amorphous state of protectant matrices. Freeze-dried matrices contain cells entrapped in the protective matrices in the freezing process. The retention of viability during storage seems to be controlled by water plasticization of the protectant matrix and possibly interactions of water with the dehydrated cells. Highest cell viability was obtained in glassy protective media. This study shows that physicochemical properties of protective media affect the stability of dehydrated cultures. Trehalose and lactose may be used in combination, which is particularly important for the stabilization of probiotic bacteria in dairy

  3. Uncertainty analysis as essential step in the establishment of the dynamic Design Space of primary drying during freeze-drying.

    PubMed

    Mortier, Séverine Thérèse F C; Van Bockstal, Pieter-Jan; Corver, Jos; Nopens, Ingmar; Gernaey, Krist V; De Beer, Thomas

    2016-06-01

    Large molecules, such as biopharmaceuticals, are considered the key driver of growth for the pharmaceutical industry. Freeze-drying is the preferred way to stabilise these products when needed. However, it is an expensive, inefficient, time- and energy-consuming process. During freeze-drying, there are only two main process variables to be set, i.e. the shelf temperature and the chamber pressure, however preferably in a dynamic way. This manuscript focuses on the essential use of uncertainty analysis for the determination and experimental verification of the dynamic primary drying Design Space for pharmaceutical freeze-drying. Traditionally, the chamber pressure and shelf temperature are kept constant during primary drying, leading to less optimal process conditions. In this paper it is demonstrated how a mechanistic model of the primary drying step gives the opportunity to determine the optimal dynamic values for both process variables during processing, resulting in a dynamic Design Space with a well-known risk of failure. This allows running the primary drying process step as time efficient as possible, hereby guaranteeing that the temperature at the sublimation front does not exceed the collapse temperature. The Design Space is the multidimensional combination and interaction of input variables and process parameters leading to the expected product specifications with a controlled (i.e., high) probability. Therefore, inclusion of parameter uncertainty is an essential part in the definition of the Design Space, although it is often neglected. To quantitatively assess the inherent uncertainty on the parameters of the mechanistic model, an uncertainty analysis was performed to establish the borders of the dynamic Design Space, i.e. a time-varying shelf temperature and chamber pressure, associated with a specific risk of failure. A risk of failure acceptance level of 0.01%, i.e. a 'zero-failure' situation, results in an increased primary drying process time

  4. Impact of Ice Morphology on Design Space of Pharmaceutical Freeze-Drying.

    PubMed

    Goshima, Hiroshika; Do, Gabsoo; Nakagawa, Kyuya

    2016-06-01

    It has been known that the sublimation kinetics of a freeze-drying product is affected by its internal ice crystal microstructures. This article demonstrates the impact of the ice morphologies of a frozen formulation in a vial on the design space for the primary drying of a pharmaceutical freeze-drying process. Cross-sectional images of frozen sucrose-bovine serum albumin aqueous solutions were optically observed and digital pictures were acquired. Binary images were obtained from the optical data to extract the geometrical parameters (i.e., ice crystal size and tortuosity) that relate to the mass-transfer resistance of water vapor during the primary drying step. A mathematical model was used to simulate the primary drying kinetics and provided the design space for the process. The simulation results predicted that the geometrical parameters of frozen solutions significantly affect the design space, with large and less tortuous ice morphologies resulting in wide design spaces and vice versa. The optimal applicable drying conditions are influenced by the ice morphologies. Therefore, owing to the spatial distributions of the geometrical parameters of a product, the boundary curves of the design space are variable and could be tuned by controlling the ice morphologies. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Determination of mass and heat transfer parameters during freeze-drying cycles of pharmaceutical products.

    PubMed

    Hottot, A; Vessot, S; Andrieu, J

    2005-01-01

    The principal aim of this study was to evaluate the water vapour mass transfer resistance of the dried layer and the vial heat transfer coefficient values of a pharmaceutical product during the primary drying period. First, overall vial heat transfer coefficient values, Kv, were determined by a gravimetric method based on pure ice sublimation experiments. Thus, it was possible to set up a map of the total heat flux received by each vial throughout the plate surface of our pilot scale freeze-dryer. Important heterogeneities were observed for the vials placed at the plate edges and for the vials placed at the center of the plate. As well, the same gravimetric method was also used to precisely determine the influence of main lyophilization operating parameters (shelf temperature and gas total pressure) or the vial types and sizes on these overall heat transfer coefficient values. A semi-empirical relationship as a function of total gas pressure was proposed. The transient method by pressure rise analysis (PRA method) after interrupting the water vapour flow between the sublimation chamber and the condenser, previously set up and validated in our laboratory, was then extensively used with an amorphous BSA-based formulation to identify the dried layer mass transfer resistance values, Rp, the ice front temperature, and the total heat transfer coefficient values, Kv, with or without annealing treatment. It was proved that this method gave accurate and coherent data only during the first half of the sublimation period when the totality of the vials of the set was still sublimating. Thus, this rapid method allowed estimation of, on line and in situ, the sublimation front temperature and the characterization of the morphology and structure of the freeze-dried layer, all along the first part of the sublimation period. The estimated sublimation temperatures shown by the PRA model were about 2 degrees C lower than the experimental values obtained using thermocouples inserted

  6. Effective Porosity Measurements by Wet- and Dry-type Vacuum Saturations using Process-Programmable Vacuum Saturation System

    NASA Astrophysics Data System (ADS)

    Lee, T. J.; Lee, K. S., , Dr; Lee, S. K.

    2017-12-01

    One of the most important factors in measuring effective porosity by vacuum saturation method is that the air in the pore space can be fully substituted by water during the vacuum saturation process. International Society of Rock Mechanics (ISRM) suggests vacuuming a rock sample submerged in the water, while American Society of Test and Materials (ASTM) vacuuming the sample and water separately and then pour the water to the sample. In this study, we call the former wet-type vacuum saturation (WVS) method and the latter dry-type vacuum saturation (DVS) method, and compare the effective porosity measured by the two different vacuum saturation processes. For that purpose, a vacuum saturation system has been developed, which can support both WVS and DVS by only changing the process by programming. Comparison of effective porosity has been made for a cement mortar and rock samples. As a result, DVS can substitute more void volume to water than WVS, which in turn insists that DVS can provide more exact value of effective porosity than WVS.

  7. [A case of orchitis following vaccination with freeze-dried live attenuated mumps vaccine].

    PubMed

    Suzuki, Masayasu; Takizawa, Akitoshi; Furuta, Akira; Yanada, Shuichi; Iwamuro, Shinya; Tashiro, Kazuya

    2002-05-01

    In Japan, freeze-dried live attenuated mumps vaccine has been used optionally since 1981. The effectiveness of mumps vaccination has been established by worldwide research since 1971. On the other hand, because of it's live activity several untoward effects have been reported. Vaccination-related mumps orchitis is a rare adverse effect of mumps vaccine. Only 9 cases of vaccination-related mumps orchitis have been reported in Japan. We describe a case of orchitis following mumps vaccination in adolescence. A 16 years-old male has admitted because of acute orchitis with high fever and painful swelling of right testis. The patient had received vaccination with freeze-dried live attenuated mumps vaccine 16 days before admission. After admission, the bed-rest had completely relieved the symptoms on 6th hospital day. The impaired testis has maintained normal size and consistency 6 months after discharge.

  8. Pre-cure freezing affects proteolysis in dry-cured hams.

    PubMed

    Bañón, S; Cayuela, J M; Granados, M V; Garrido, M D

    1999-01-01

    Several parameters (sodium chloride, moisture, intramuscular fat, total nitrogen, non-protein nitrogen, white precipitates, free tyrosine, L* a* b* values and acceptability) related with proteolysis during the curing were compared in dry-cured hams manufactured from refrigerated and frozen/thawed raw material. Pre-cure freezing increased the proteolysis levels significantly (p<0.05) in the zones of the ham where water losses and absorption of salt is slowest. Frozen hams present a high incidence of white precipitates, formed mainly by tyrosine crystals. The colour and acceptability scores are similar in frozen and refrigerated hams. The previous freezing and thawing process accentuates the water losses, salt absorption and proteolysis of the cured meat, although it does not significantly affect the sensory quality of the dry-cured ham.

  9. [A case of freeze-dried gas gangrene antitoxin for the treatment of Clostridium perfringens sepsis].

    PubMed

    Yoshida, Juichiro; Nakamura, Hideki; Yamada, Shinya; Sekoguchi, Satoru; Suzuki, Takahiro; Tomatsuri, Naoya; Sato, Hideki; Okuyama, Yusuke; Kimura, Hiroyuki; Yoshida, Norimasa

    2015-02-01

    A 66-year-old man was admitted to our hospital with high fever. We diagnosed a gas-containing liver abscess and performed percutaneous abscess drainage. However, 15 hours after admission, he developed massive intravascular hemolysis and acidosis. Sepsis due to Clostridium perfringens was suspected and we treated the patient intensively with multidisciplinary approaches, including antibiotics, mechanical ventilation, and renal replacement therapy. Furthermore, we administered freeze-dried gas gangrene antitoxin. Despite intensive care, the patient died 43 hours after admission.

  10. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production

    PubMed Central

    Kanojia, Gaurav; Have, Rimko ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W.; Kersten, Gideon F. A.; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn’s disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab. PMID:27706175

  11. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production.

    PubMed

    Kanojia, Gaurav; Have, Rimko Ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W; Kersten, Gideon F A; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab.

  12. Naproxen Microparticulate Systems Prepared Using In Situ Crystallisation and Freeze-Drying Techniques.

    PubMed

    Solaiman, Amanda; Tatari, Adam Keenan; Elkordy, Amal Ali

    2017-07-01

    Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient.

  13. Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers.

    PubMed

    Wang, Lulu; Ma, Yingying; Gu, Yu; Liu, Yangyang; Zhao, Juan; Yan, Beibei; Wang, Yancai

    2018-04-19

    Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6-8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.

  14. Filament organization revealed in platinum replicas of freeze-dried cytoskeletons

    PubMed Central

    1980-01-01

    This report presents the appearance of rapidly frozen, freeze-dried cytoskeletons that have been rotary replicated with platinum and viewed in the transmission electron microscope. The resolution of this method is sufficient to visualize individual filaments in the cytoskeleton and to discriminate among actin, microtubules, and intermediate filaments solely by their surface substructure. This identification has been confirmed by specific decoration with antibodies and selective extraction of individual filament types, and correlated with light microscope immunocytochemistry and gel electrophoresis patterns. The freeze-drying preserves a remarkable degree of three-dimensionality in the organization of these cytoskeletons. They look strikingly similar to the meshwork of strands or "microtrabeculae" seen in the cytoplasm of whole cells by high voltage electron microscopy, in that the filaments form a lattice of the same configutation and with the same proportions of open area as the microtrabeculae seen in whole cells. The major differences between these two views of the structural elements of the cytoplasmic matrix can be attributed to the effects of aldehyde fixation and dehydration. Freeze-dried cytoskeletons thus provide an opportunity to study--at high resolution and in the absence of problems caused by chemical fixation--the detailed organization of filaments in different regions of the cytoplasm and at different stages of cell development. In this report the pattern of actin and intermediate filament organization in various regions of fully spread mouse fibroblasts is described. PMID:6893451

  15. Fuzzy Logic-based expert system for evaluating cake quality of freeze-dried formulations.

    PubMed

    Trnka, Hjalte; Wu, Jian X; Van De Weert, Marco; Grohganz, Holger; Rantanen, Jukka

    2013-12-01

    Freeze-drying of peptide and protein-based pharmaceuticals is an increasingly important field of research. The diverse nature of these compounds, limited understanding of excipient functionality, and difficult-to-analyze quality attributes together with the increasing importance of the biosimilarity concept complicate the development phase of safe and cost-effective drug products. To streamline the development phase and to make high-throughput formulation screening possible, efficient solutions for analyzing critical quality attributes such as cake quality with minimal material consumption are needed. The aim of this study was to develop a fuzzy logic system based on image analysis (IA) for analyzing cake quality. Freeze-dried samples with different visual quality attributes were prepared in well plates. Imaging solutions together with image analytical routines were developed for extracting critical visual features such as the degree of cake collapse, glassiness, and color uniformity. On the basis of the IA outputs, a fuzzy logic system for analysis of these freeze-dried cakes was constructed. After this development phase, the system was tested with a new screening well plate. The developed fuzzy logic-based system was found to give comparable quality scores with visual evaluation, making high-throughput classification of cake quality possible. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Controlling the physical form of mannitol in freeze-dried systems.

    PubMed

    Mehta, Mehak; Bhardwaj, Sunny P; Suryanarayanan, Raj

    2013-10-01

    A potential drawback with the use of mannitol as a bulking agent is its existence as mannitol hemihydrate (MHH; C₆H₁₄O₆·0.5H₂O) in the lyophile. Once formed during freeze-drying, MHH dehydration may require secondary drying under aggressive conditions which can be detrimental to the stability of thermolabile components. If MHH is retained in the lyophile, the water released by MHH dehydration during storage has the potential to cause product instability. We systematically identified the conditions under which anhydrous mannitol and MHH crystallized in frozen systems with the goal of preventing MHH formation during freeze-drying. When mannitol solutions were cooled, the temperature of solute crystallization was the determinant of the physical form of mannitol. Based on low temperature X-ray diffractometry (using both laboratory and synchrotron sources), MHH formation was observed when solute crystallization occurred at temperatures ≤ -20 °C, while anhydrous mannitol crystallized at temperatures ≤ -10 °C. The transition temperature (anhydrate - MHH) appears to be ∼-15 °C. The use of a freeze-dryer with controlled ice nucleation technology enabled anhydrous mannitol crystallization at ∼-5 °C. Thus, ice crystallization followed by annealing at temperatures ≤ -10 °C can be an effective strategy to prevent MHH formation. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Water-Hydrogel Binding Affinity Modulates Freeze-Drying-Induced Micropore Architecture and Skeletal Myotube Formation.

    PubMed

    Rich, Max H; Lee, Min Kyung; Marshall, Nicholas; Clay, Nicholas; Chen, Jinrong; Mahmassani, Ziad; Boppart, Marni; Kong, Hyunjoon

    2015-08-10

    Freeze-dried hydrogels are increasingly used to create 3D interconnected micropores that facilitate biomolecular and cellular transports. However, freeze-drying is often plagued by variance in micropore architecture based on polymer choice. We hypothesized that water-polymer binding affinity plays a significant role in sizes and numbers of micropores formed through freeze-drying, influencing cell-derived tissue quality. Poly(ethylene glycol)diacrylate (PEGDA) hydrogels with alginate methacrylate (AM) were used due to AM's higher binding affinity for water than PEGDA. PEGDA-AM hydrogels with larger AM concentrations resulted in larger sizes and numbers of micropores than pure PEGDA hydrogels, attributed to the increased mass of water binding to the PEGDA-AM gel. Skeletal myoblasts loaded in microporous PEGDA-AM hydrogels were active to produce 3D muscle-like tissue, while those loaded in pure PEGDA gels were localized on the gel surface. We propose that this study will be broadly useful in designing and improving the performance of various microporous gels.

  18. Use of manometric temperature measurements (MTM) to characterize the freeze-drying behavior of amorphous protein formulations.

    PubMed

    Johnson, Robert E; Oldroyd, Megan E; Ahmed, Saleem S; Gieseler, Henning; Lewis, Lavinia M

    2010-06-01

    The freeze-drying behavior and cake morphology of a model protein in an amorphous formulation were studied at varying protein concentrations using conservative (-25 degrees C) and aggressive (+25 degrees C) shelf temperatures at constant chamber pressure during primary drying. The two cycles were characterized by manometric temperature measurements (MTM) in a SMART freeze dryer that estimates the sublimation rate (dm/dt), product temperature at the freeze-drying front (T(p-MTM)) and product resistance (R(p)) during a run. The calculated sublimation rates (dm/dt) were 3-4 times faster in the aggressive cycle compared to the conservative cycle. For conservatively dried cakes R(p) increased with both dry layer thickness and protein concentration. For aggressively dried cakes (where freeze-drying occurs at the edge of microcollapse), R(p) also increased with protein concentration but was independent of the dry layer thickness. The sublimation rate was influenced by R(p), dry layer thickness and T(p-MTM) in the conservative cycle, but was governed mainly by T(p-MTM) in the aggressive cycle, where R(p) is independent of the dry layer thickness. The aggressively dried cakes had a more open and porous structure compared to their conservatively dried counterparts. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  19. Effects of drying-wetting and freezing-thawing cycle on leachability of metallic elements in mine soils

    NASA Astrophysics Data System (ADS)

    Bang, H.; Kim, J.; Hyun, S.

    2016-12-01

    Mine leachate derived from contaminated mine sites with metallic elements can pose serious risks on human society and environment. Only labile fraction of metallic elements in mine soils is subject to leaching and movement by rainfall. Lability of metallic element in soil is a function of bond strengths between metal and soil surfaces, which is influenced by environmental condition (e.g., rainfall intensity, duration, temperature, etc.) The purpose of this study was to elucidate the effects of various climate conditions on the leaching patterns and lability of metallic elements in mine soils. To do this, two mine soils were sampled from two abandoned mine sites located in Korea. Leaching test were conducted using batch decant-refill method. Various climatic conditions were employed in leaching test such as (1) oven drying (40oC) - wetting cycles, (2) air drying (20oC) - wetting cycle, and (3) freezing (-40oC) - thawing cycles. Duration of drying and freezing were varied from 4 days to 2 weeks. Concentration of metallic elements, pH, Eh and concentration of dissolved iron and sulfate in leachate from each leaching process was measured. To identify the changes of labile fraction in mine soils after each of drying or freezing period, sequential extraction procedure (five fraction) was used to compare labile fraction (i.e., F1 + F2) of metallic elements. The concentration of metallic elements in mine leachate was increased after drying and freezing procedure. The amounts of released metallic element from mine soils was changed depending on their drying or freezing period. In addition, labile fraction of metallic elements in soil was also changed after drying and freezing. The changes in labile fraction after drying and freezing might be due to the increased soil surface area by pore water volume expansion. Further study is therefore needed to evaluate the impact of altered physical properties of soils such as hydration of soil surface area and shrinking by drying and

  20. Novel Budesonide Particles for Dry Powder Inhalation Prepared Using a Microfluidic Reactor Coupled With Ultrasonic Spray Freeze Drying.

    PubMed

    Saboti, Denis; Maver, Uroš; Chan, Hak-Kim; Planinšek, Odon

    2017-07-01

    Budesonide (BDS) is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers, nebulizers, and dry powder inhalers. Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine BDS particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol-water, methanol-water, and an acetone-water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result was fine crystalline BDS powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6% ± 2.8% to 54.9% ± 1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  1. Rapid formation of phase-clean 110 K (Bi-2223) powders derived via freeze-drying process

    DOEpatents

    Balachandran, Uthamalingam

    1996-01-01

    A process for the preparation of amorphous precursor powders for Pb-doped Bi.sub.2 Sr.sub.2 Ca.sub.2 Cu.sub.3 O.sub.x (2223) includes a freeze-drying process incorporating a splat-freezing step. The process generally includes splat freezing a nitrate solution of Bi, Pb, Sr, Ca, and Cu to form flakes of the solution without any phase separation; grinding the frozen flakes to form a powder; freeze-drying the frozen powder; heating the dried powder to form a dry green precursor powders; denitrating the green-powders; heating the denitrated powders to form phase-clean Bi-2223 powders. The grain boundaries of the 2223 grains appear to be clean, leading to good intergrain contact between 2223 grains.

  2. Rapid formation of phase-clean 110 K (Bi-2223) powders derived via freeze-drying process

    DOEpatents

    Balachandran, U.

    1996-06-04

    A process for the preparation of amorphous precursor powders for Pb-doped Bi{sub 2}Sr{sub 2} Ca{sub 2}Cu{sub 3}O{sub x} (2223) includes a freeze-drying process incorporating a splat-freezing step. The process generally includes splat freezing a nitrate solution of Bi, Pb, Sr, Ca, and Cu to form flakes of the solution without any phase separation; grinding the frozen flakes to form a powder; freeze-drying the frozen powder; heating the dried powder to form a dry green precursor powders; denitrating the green-powders; heating the denitrated powders to form phase-clean Bi-2223 powders. The grain boundaries of the 2223 grains appear to be clean, leading to good intergrain contact between 2223 grains. 11 figs.

  3. Production of inhalation phage powders using spray freeze drying and spray drying techniques for treatment of respiratory infections

    PubMed Central

    Leung, Sharon S.Y.; Parumasivam, Thaigarajan; Gao, Fiona G.; Carrigy, Nicholas B.; Vehring, Reinhard; Finlay, Warren H.; Morales, Sandra; Britton, Warwick J; Kutter, Elizabeth; Chan, Hak-Kim

    2016-01-01

    Purpose The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. Method A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. Results A significant titer loss (~ 2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 104 pfu and SD-F2 = 11.0 ± 1.4 × 104 pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 104 pfu and SFD-F2 = 2.1 ± 0.3 × 104 pfu). Conclusion Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2. PMID:26928668

  4. Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.

    PubMed

    Ma, Yue-Qin; Zhang, Zeng-Zhu; Li, Gang; Zhang, Jing; Xiao, Han-Yang; Li, Xian-Fei

    2016-03-01

    To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.

  5. Experimental determination of the key heat transfer mechanisms in pharmaceutical freeze-drying.

    PubMed

    Ganguly, Arnab; Nail, Steven L; Alexeenko, Alina

    2013-05-01

    The study is aimed at quantifying the relative contribution of key heat transfer modes in lyophilization. Measurements of vial heat transfer rates in a laboratory-scale freeze-dryer were performed using pure water, which was partially sublimed under various conditions. The separation distance between the shelf and the vial was systematically varied, and sublimation rates were determined gravimetrically. The heat transfer rates were observed to be independent of separation distance between the vial and the shelf and linearly dependent on pressure in the free molecular flow limit, realized at low pressures (<50 mTorr). However, under higher pressures (>120 mTorr), heat transfer rates were independent of pressure and inversely proportional to separation distance. Previous heat transfer studies in conventional freeze-drying cycles have attributed a dominant portion of the total heat transfer to radiation, the rest to conduction, whereas convection has been found to be insignificant. Although the measurements reported here confirm the significance of the radiative and gas conduction components, the convective component has been found to be comparable to the gas conduction contribution at pressures greater than 100 mTorr. The current investigation supports the conclusion that the convective component of the heat transfer cannot be ignored in typical laboratory-scale freeze-drying conditions. Copyright © 2013 Wiley Periodicals, Inc.

  6. Optimization of a protective medium for freeze-dried Pichia membranifaciens and application of this biocontrol agent on citrus fruit.

    PubMed

    Niu, X; Deng, L; Zhou, Y; Wang, W; Yao, S; Zeng, K

    2016-07-01

    To optimize a protective medium for freeze-dried Pichia membranifaciens and to evaluate biocontrol efficacies of agents against blue and green mould and anthracnose in citrus fruit. Based on the screening assays of saccharides and antioxidants, response surface methodology was used to optimize sucrose, sodium glutamate and skim milk to improve viability of freeze-dried Pi. membranifaciens. Biocontrol assays were conducted between fresh and freeze-dried Pi. membranifaciens against Penicillium italicum, Penicillium digitatum and Colletotrichum gloeosporioides in citrus fruit. Solving the regression equation indicated that the optimal protective medium was 6·06% (w/v) sucrose combined with 3·40% (w/v) sodium glutamate and 5·43% (w/v) skim milk. Pi. membranifaciens freeze-dried in the optimal protective medium showed 76·80% viability, and retained biocontrol efficacy against Pe. italicum, Pe. digitatum and Co. gloeosporioides in citrus fruit. The optimal protective medium showed more effective protective properties than each of the three protectants used alone. The viability of freeze-dried Pi. membranifaciens finally reached 76·80%. Meanwhile, the biocontrol efficacies showed no significant difference between fresh and freeze-dried yeast against Pe. italicum, Pe. digitatum and Co. gloeosporioides in citrus fruit. The results showed the potential value of Pi. membranifaciens CICC 32259 for commercialization. © 2016 The Society for Applied Microbiology.

  7. Freeze-dried, mucoadhesive system for vaginal delivery of the HIV microbicide, dapivirine: optimisation by an artificial neural network.

    PubMed

    Woolfson, A David; Umrethia, Manish L; Kett, Victoria L; Malcolm, R Karl

    2010-03-30

    Dapivirine mucoadhesive gels and freeze-dried tablets were prepared using a 3x3x2 factorial design. An artificial neural network (ANN) with multi-layer perception was used to investigate the effect of hydroxypropyl-methylcellulose (HPMC): polyvinylpyrrolidone (PVP) ratio (X1), mucoadhesive concentration (X2) and delivery system (gel or freeze-dried mucoadhesive tablet, X3) on response variables; cumulative release of dapivirine at 24h (Q(24)), mucoadhesive force (F(max)) and zero-rate viscosity. Optimisation was performed by minimising the error between the experimental and predicted values of responses by ANN. The method was validated using check point analysis by preparing six formulations of gels and their corresponding freeze-dried tablets randomly selected from within the design space of contour plots. Experimental and predicted values of response variables were not significantly different (p>0.05, two-sided paired t-test). For gels, Q(24) values were higher than their corresponding freeze-dried tablets. F(max) values for freeze-dried tablets were significantly different (2-4 times greater, p>0.05, two-sided paired t-test) compared to equivalent gels. Freeze-dried tablets having lower values for X1 and higher values for X2 components offered the best compromise between effective dapivirine release, mucoadhesion and viscosity such that increased vaginal residence time was likely to be achieved. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  8. The Effect of Freeze-Drying on the Nutrient, Polyphenol, and Oxidant Levels of Breast Milk.

    PubMed

    Cortez, Mariela Valentina; Soria, Elio Andrés

    2016-12-01

    Human milk banks need to extend the suitability of milk for breastfeeding, and for this technological advances are required. Our aim was to establish the capacity of freeze-drying to conserve milk properties without further oxidative deterioration. One hundred sixteen healthy women participated from the city of Cordoba (Argentina). Proteins, glucose, triglycerides, polyphenols, and markers (nitrites, superoxide anion, hydroperoxides, lipoperoxides, and γ-glutamyl transpeptidase) were measured in their fresh milk. Samples were then separated for three treatments as follows: freezing and conservation for 6 months at -80°C (F: positive control); freeze-drying for 24 hours at ≤-70°C and ≤1.33 Pa and conservation for 6 months at 4°C (FD: treatment of interest); and freeze-drying for 24 hours at ≤-70°C and ≤1.33 Pa and conservation for 6 months at -80°C (FD+F). Next, analyses were repeated and compared by ANOVA and Tukey tests. Fresh milk showed these values per L as follows: proteins: 12.62 ± 2.51 g, glucose: 4.44 ± 0.25 g, triglycerides: 34.26 ± 0.59 g, polyphenols: 53.27 ± 8.67 mg, nitrites: 62.40 ± 19.09 mg, superoxide: 3,721.02 ± 198.80 OD, hydroperoxides: 7,343.76 ± 294.53 OD, lipoperoxides: 7,349.72 ± 398.72 OD, and γ-glutamyl transpeptidase: 4.66 ± 0.55 IU. Glucose was decreased after F treatment (p < 0.05), all variables were conserved by FD and were not improved by the FD + F combination. Freeze-drying achieved suitable conservation and may improve bank functioning, by protecting nutritional properties, polyphenol-related functionality, and oxidative integrity of human milk through a 1-day treatment with easy maintenance.

  9. The Change of Total Anthocyanins in Blueberries and Their Antioxidant Effect After Drying and Freezing

    PubMed Central

    Srzednicki, George

    2004-01-01

    This study examined the effects of freezing, storage, and cabinet drying on the anthocyanin content and antioxidant activity of blueberries (Vaccinium corymbosum L). Fresh samples were stored for two weeks at 5°C while frozen samples were kept for up to three months at −20°C. There were two drying treatments, one including osmotic pretreatment followed by cabinet drying and the other involving only cabinet drying. Total anthocyanins found in fresh blueberries were 7.2 ± 0.5 mg/g dry matter, expressed as cyanidin 3-rutinoside equivalents. In comparison with fresh samples, total anthocyanins in untreated and pretreated dried blueberries were significantly reduced to 4.3 ± 0.1 mg/g solid content, 41% loss, and 3.7 ± 0.2 mg/g solid content, 49% loss, respectively. Osmotic treatment followed by a thermal treatment had a greater effect on anthocyanin loss than the thermal treatment alone. In contrast, the frozen samples did not show any significant decrease in anthocyanin level during three months of storage. Measurement of the antioxidant activity of anthocyanin extracts from blueberries showed there was no significant difference between fresh, dried, and frozen blueberries. PMID:15577185

  10. Stabilities of Dried Suspensions of Influenza Virus Sealed in a Vacuum or Under Different Gases

    PubMed Central

    Greiff, Donald; Rightsel, Wilton A.

    1969-01-01

    Suspensions of purified influenza virus, dried to a 1.4% content of residual moisture by sublimation of ice in vacuo, were sealed in a vacuum or under different gases of high purity. The stabilities of the several preparations were determined by an accelerated storage test. Based on the times predicted for the dried preparations stored at different temperatures to lose 1 log of infectivity titer, the order of stabilities in relation to sealing in vacuum or under different gases was as follows: helium > hydrogen > vacuum > argon > nitrogen > oxygen > carbon dioxide. Images PMID:5797938

  11. Depositing nanoparticles on a silicon substrate using a freeze drying technique.

    PubMed

    Sigehuzi, Tomoo

    2017-08-28

    For the microscopic observation of nanoparticles, an adequate sample preparation is an essential part of this task. Much research has been performed for usable preparation methods that will yield aggregate-free samples. A freeze drying technique, which only requires a -80  ° C freezer and a freeze dryer, is shown to provide an on-substrate dispersion of mostly isolated nanoparticles. The particle density could be made sufficiently high for efficient observations using atomic force microscopy. Since this sandwich method is purely physical, it could be applied to deposit various nanoparticles independent of their surface chemical properties. Suspension film thickness, or the dimensionality of the suspension film, was shown to be crucial for the isolation of the particles. Silica nanoparticles were dispersed on a silicon substrate using this method and the sample properties were examined using atomic force microscopy.

  12. Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds

    PubMed Central

    Adler, Gabriela; Koop, Thomas; Haspel, Carynelisa; Taraniuk, Ilya; Moise, Tamar; Koren, Ilan; Heiblum, Reuven H.; Rudich, Yinon

    2013-01-01

    The cycling of atmospheric aerosols through clouds can change their chemical and physical properties and thus modify how aerosols affect cloud microphysics and, subsequently, precipitation and climate. Current knowledge about aerosol processing by clouds is rather limited to chemical reactions within water droplets in warm low-altitude clouds. However, in cold high-altitude cirrus clouds and anvils of high convective clouds in the tropics and midlatitudes, humidified aerosols freeze to form ice, which upon exposure to subsaturation conditions with respect to ice can sublimate, leaving behind residual modified aerosols. This freeze-drying process can occur in various types of clouds. Here we simulate an atmospheric freeze-drying cycle of aerosols in laboratory experiments using proxies for atmospheric aerosols. We find that aerosols that contain organic material that undergo such a process can form highly porous aerosol particles with a larger diameter and a lower density than the initial homogeneous aerosol. We attribute this morphology change to phase separation upon freezing followed by a glass transition of the organic material that can preserve a porous structure after ice sublimation. A porous structure may explain the previously observed enhancement in ice nucleation efficiency of glassy organic particles. We find that highly porous aerosol particles scatter solar light less efficiently than nonporous aerosol particles. Using a combination of satellite and radiosonde data, we show that highly porous aerosol formation can readily occur in highly convective clouds, which are widespread in the tropics and midlatitudes. These observations may have implications for subsequent cloud formation cycles and aerosol albedo near cloud edges. PMID:24297908

  13. Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds.

    PubMed

    Adler, Gabriela; Koop, Thomas; Haspel, Carynelisa; Taraniuk, Ilya; Moise, Tamar; Koren, Ilan; Heiblum, Reuven H; Rudich, Yinon

    2013-12-17

    The cycling of atmospheric aerosols through clouds can change their chemical and physical properties and thus modify how aerosols affect cloud microphysics and, subsequently, precipitation and climate. Current knowledge about aerosol processing by clouds is rather limited to chemical reactions within water droplets in warm low-altitude clouds. However, in cold high-altitude cirrus clouds and anvils of high convective clouds in the tropics and midlatitudes, humidified aerosols freeze to form ice, which upon exposure to subsaturation conditions with respect to ice can sublimate, leaving behind residual modified aerosols. This freeze-drying process can occur in various types of clouds. Here we simulate an atmospheric freeze-drying cycle of aerosols in laboratory experiments using proxies for atmospheric aerosols. We find that aerosols that contain organic material that undergo such a process can form highly porous aerosol particles with a larger diameter and a lower density than the initial homogeneous aerosol. We attribute this morphology change to phase separation upon freezing followed by a glass transition of the organic material that can preserve a porous structure after ice sublimation. A porous structure may explain the previously observed enhancement in ice nucleation efficiency of glassy organic particles. We find that highly porous aerosol particles scatter solar light less efficiently than nonporous aerosol particles. Using a combination of satellite and radiosonde data, we show that highly porous aerosol formation can readily occur in highly convective clouds, which are widespread in the tropics and midlatitudes. These observations may have implications for subsequent cloud formation cycles and aerosol albedo near cloud edges.

  14. Improvement of fish freshness determination method by the application of amorphous freeze-dried enzymes.

    PubMed

    Srirangsan, Paveena; Hamada-Sato, Naoko; Kawai, Kiyoshi; Watanabe, Manabu; Suzuki, Toru

    2010-12-08

    Alkaline phosphatase (ALP), nucleoside phosphorylase (NP), and xanthine oxidase (XOD) were used in a colorimetric method for evaluation of fish freshness based on the Ki value. Two enzyme mixtures, NP-XOD and ALP-NP-XOD, were prepared with a color developing agent, and stabilities of the enzymes were improved by freeze-drying with glass-forming additives, i.e., sucrose and sucrose-gelatin. As a result, a linear relationship was obtained between the Ki values determined by the developed colorimetric method and a conventional high-performance liquid chromatography with a high correlation coefficient of 0.997. All enzyme samples containing the additive(s) were amorphous, and higher enzymes activities were maintained compared to those freeze-dried without an additive. Sucrose-gelatin/enzyme mixtures showed higher glass transition temperature; consequently, the enzymes were better stabilized than the sucrose/enzyme formulations. Using the sucrose-gelatin/enzyme mixture, Ki values of fish meat could be accurately determined even after 6-month storage of the dried enzymes at 40 °C.

  15. Large scale synthesis of nanostructured zirconia-based compounds from freeze-dried precursors

    SciT

    Gomez, A.; Villanueva, R.; Vie, D.

    2013-01-15

    Nanocrystalline zirconia powders have been obtained at the multigram scale by thermal decomposition of precursors resulting from the freeze-drying of aqueous acetic solutions. This technique has equally made possible to synthesize a variety of nanostructured yttria or scandia doped zirconia compositions. SEM images, as well as the analysis of the XRD patterns, show the nanoparticulated character of those solids obtained at low temperature, with typical particle size in the 10-15 nm range when prepared at 673 K. The presence of the monoclinic, the tetragonal or both phases depends on the temperature of the thermal treatment, the doping concentration and themore » nature of the dopant. In addition, Rietveld refinement of the XRD profiles of selected samples allows detecting the coexistence of the tetragonal and the cubic phases for high doping concentration and high thermal treatment temperatures. Raman experiments suggest the presence of both phases also at relatively low treatment temperatures. - Graphical abstract: Zr{sub 1-x}A{sub x}O{sub 2-x/2} (A=Y, Sc; 0{<=}x{<=}0.12) solid solutions have been prepared as nanostructured powders by thermal decomposition of precursors obtained by freeze-drying, and this synthetic procedure has been scaled up to the 100 g scale. Highlights: Black-Right-Pointing-Pointer Zr{sub 1-x}A{sub x}O{sub 2-x/2} (A=Y, Sc; 0{<=}x{<=}0.12) solid solutions have been prepared as nanostructured powders. Black-Right-Pointing-Pointer The synthetic method involves the thermal decomposition of precursors obtained by freeze-drying. Black-Right-Pointing-Pointer The temperature of the thermal treatment controls particle sizes. Black-Right-Pointing-Pointer The preparation procedure has been scaled up to the 100 g scale. Black-Right-Pointing-Pointer This method is appropriate for the large-scale industrial preparation of multimetallic systems.« less

  16. Process analytical technologies (PAT) in freeze-drying of parenteral products.

    PubMed

    Patel, Sajal Manubhai; Pikal, Michael

    2009-01-01

    Quality by Design (QbD), aims at assuring quality by proper design and control, utilizing appropriate Process Analytical Technologies (PAT) to monitor critical process parameters during processing to ensure that the product meets the desired quality attributes. This review provides a comprehensive list of process monitoring devices that can be used to monitor critical process parameters and will focus on a critical review of the viability of the PAT schemes proposed. R&D needs in PAT for freeze-drying have also been addressed with particular emphasis on batch techniques that can be used on all the dryers independent of the dryer scale.

  17. Annealing to optimize the primary drying rate, reduce freezing-induced drying rate heterogeneity, and determine T(g)' in pharmaceutical lyophilization.

    PubMed

    Searles, J A; Carpenter, J F; Randolph, T W

    2001-07-01

    In a companion paper we show that the freezing of samples in vials by shelf-ramp freezing results in significant primary drying rate heterogeneity because of a dependence of the ice crystal size on the nucleation temperature during freezing.1 The purpose of this study was to test the hypothesis that post-freezing annealing, in which the product is held at a predetermined temperature for a specified duration, can reduce freezing-induced heterogeneity in sublimation rates. In addition, we test the impact of annealing on primary drying rates. Finally, we use the kinetics of relaxations during annealing to provide a simple measurement of T(g)', the glass transition temperature of the maximally freeze-concentrated amorphous phase, under conditions and time scales most appropriate for industrial lyophilization cycles. Aqueous solutions of hydroxyethyl starch (HES), sucrose, and HES:sucrose were either frozen by placement on a shelf while the temperature was reduced ("shelf-ramp frozen") or by immersion into liquid nitrogen. Samples were then annealed for various durations over a range of temperatures and partially lyophilized to determine the primary drying rate. The morphology of fully dried liquid nitrogen-frozen samples was examined using scanning electron microscopy. Annealing reduced primary drying rate heterogeneity for shelf-ramp frozen samples, and resulted in up to 3.5-fold increases in the primary drying rate. These effects were due to increased ice crystal sizes, simplified amorphous structures, and larger and more numerous holes on the cake surface of annealed samples. Annealed HES samples dissolved slightly faster than their unannealed counterparts. Annealing below T(g)' did not result in increased drying rates. We present a simple new annealing-lyophilization method of T(g)' determination that exploits this phenomenon. It can be carried out with a balance and a freeze-dryer, and has the additional advantage that a large number of candidate formulations can

  18. Monitoring of the secondary drying in freeze-drying of pharmaceuticals.

    PubMed

    Fissore, Davide; Pisano, Roberto; Barresi, Antonello A

    2011-02-01

    This paper is focused on the in-line monitoring of the secondary drying phase of a lyophilization process. An innovative software sensor is presented to estimate reliably the residual moisture in the product and the time required to complete secondary drying, that is, to reach the target value of the residual moisture or of the desorption rate. Such results are obtained by coupling a mathematical model of the process and the in-line measurement of the solvent desorption rate and by means of the pressure rise test or another sensors (e.g., windmills, laser sensors) that can measure the vapor flux in the drying chamber. The proposed method does not require extracting any vial during the operation or using expensive sensors to measure off-line the residual moisture. Moreover, it does not require any preliminary experiment to determine the relationship between the desorption rate and residual moisture in the product. The effectiveness of the proposed approach is demonstrated by means of experiments carried out in a pilot-scale apparatus: in this case, some vials were extracted from the drying chamber and the moisture content was measured to validate the estimations provided by the soft-sensor. Copyright © 2010 Wiley-Liss, Inc.

  19. Insulation Technology in Dry Air and Vacuum for a 72kV Low Pressured Dry Air Insulated Switchgear

    NASA Astrophysics Data System (ADS)

    Yoshida, Tadahiro; Koga, Hiromi; Harada, Takakazu; Miki, Shinichi; Arioka, Masahiro; Sato, Shinji; Yoshida, Satoru; Inoue, Naoaki; Maruyama, Akihiko; Takeuchi, Toshie

    A new 72kV rated low pressured dry air insulated switchgear applying electromagnetic actuation and function that supports CBM has been developed. First, dielectric characteristics in dry air under lightning impulse application has been investigated at bare and insulator covered electrodes. Dependence of the breakdown electric field strength on the effective area has been clarified to apply the configuration design of the insulation mold for the vacuum interrupter. In addition, moisture volume dependence on surface resistance has been clarified to decide moisture volume in gas pressure tank. Next, a new vacuum circuit breaker (VCB) has been designed. To keep dimensions from former 72kV SF6 gas insulated switchgear, distance between contacts in vacuum interrupter is needed to be shorter than that of former switchgear. Voltage withstand capability between electrodes practically designed for vacuum interrupter has been investigated under dc voltage application simulated the small capacitive current breaking test. Gap configuration including contacts and slits has been optimized and distance has been shortened 11% from former switchgear. As a result, the new low pressured dry air insulated switchgear has been designed comparably in outer size to former SF6 gas insulated switchgear. Using dry air as an insulation medium with low pressure has been able to reduce the environmental burden.

  20. Effect of drying parameters on physiochemical and sensory properties of fruit powders processed by PGSS-, Vacuum- and Spray-drying.

    PubMed

    Feguš, Urban; Žigon, Uroš; Petermann, Marcus; Knez, Željko

    2015-01-01

    Aim of this experimental work was to investigate the possibility of producing fruit powders without employing drying aid and to investigate the effect of drying temperatures on the final powder characteristics. Raw fruit materials (banana puree, strawberry puree and blueberry concentrate) were processed using three different drying techniques each operating at a different temperature conditions: vacuum-drying (-27-17 °C), Spray-drying (130-160 °C) and PGSS-drying (112-152 °C). Moisture content, total colour difference, antioxidant activity and sensory characteristics of the processed fruit powders were analysed. The results obtained from the experimental work indicate that investigated fruit powders without or with minimal addition of maltodextrin can be produced. Additionally, it was observed that an increase in process temperature results in a higher loss of colour, antioxidant activity and intensity of the flavour profile.

  1. Solubility of aluminum and silica in Spodic horizons as affected by drying and freezing

    SciT

    Simonsson, M.; Berggren, D.; Gustafsson, J.P.

    The release of toxic Al{sup 3+} is one of the most serious consequences of anthropogenic soil acidification. Therefore, the mechanisms controlling Al solubility have been a topic of intense research for more than a decade. For convenience, soil samples are often dried before storage and experimental use. However, the literature offers examples of drying that results in changes in pH, solubility of organic matter, and dissolution rates of Al. In this study, the authors examined the solubility of Al and Si in fresh soil and in soil that had been dried or deep-frozen. Five Spodosol B horizon soils were subjectedmore » to batch titrations, where portions of each soil were equilibrated with solutions with varying concentrations of acid or base added. Extractions with acid oxalate and Na pyrophosphate indicated the presence of imogolite-type materials (ITM) in three of the soils. In the other two soils most secondary solid-phase Al was associated with humic substances. Deep-freezing did not significantly change pH nor the concentration of Al or Si as compared with fresh soil. Drying, on the other hand, yielded pH increases of up to 0.3 units at a given addition of acid or base, whereas Al{sup 3+} changed only slightly, implying a higher Al solubility in all of the soils. Furthermore, dissolved silica increased by up to 200% after drying, except in a soil that almost completely lacked oxalate-extractable Si. The authors suggest that drying enhanced the dissolution of ITM by disrupting soil organic matter, thus exposing formerly coated mineral surfaces. In the soil where dissolved Si did not change with drying, it has been demonstrated that Al-humus complexes controlled Al solubility. They suggest that fissures in the organic material caused by drying may have exposed formerly occluded binding sites that had a higher Al saturation than had sites at the surface of humus particles.« less

  2. Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections.

    PubMed

    Leung, Sharon S Y; Parumasivam, Thaigarajan; Gao, Fiona G; Carrigy, Nicholas B; Vehring, Reinhard; Finlay, Warren H; Morales, Sandra; Britton, Warwick J; Kutter, Elizabeth; Chan, Hak-Kim

    2016-06-01

    The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 10(4) pfu and SD-F2 = 11.0 ± 1.4 × 10(4) pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 10(4) pfu and SFD-F2 = 2.1 ± 0.3 × 10(4) pfu). Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.

  3. Structural determinants of hydration, mechanics and fluid flow in freeze-dried collagen scaffolds.

    PubMed

    Offeddu, G S; Ashworth, J C; Cameron, R E; Oyen, M L

    2016-09-01

    Freeze-dried scaffolds provide regeneration templates for a wide range of tissues, due to their flexibility in physical and biological properties. Control of structure is crucial for tuning such properties, and therefore scaffold functionality. However, the common approach of modeling these scaffolds as open-cell foams does not fully account for their structural complexity. Here, the validity of the open-cell model is examined across a range of physical characteristics, rigorously linking morphology to hydration and mechanical properties. Collagen scaffolds with systematic changes in relative density were characterized using Scanning Electron Microscopy, X-ray Micro-Computed Tomography and spherical indentation analyzed in a time-dependent poroelastic framework. Morphologically, all scaffolds were mid-way between the open- and closed-cell models, approaching the closed-cell model as relative density increased. Although pore size remained constant, transport pathway diameter decreased. Larger collagen fractions also produced greater volume swelling on hydration, although the change in pore diameter was constant, and relatively small at ∼6%. Mechanically, the dry and hydrated scaffold moduli varied quadratically with relative density, as expected of open-cell materials. However, the increasing pore wall closure was found to determine the time-dependent nature of the hydrated scaffold response, with a decrease in permeability producing increasingly elastic rather than viscoelastic behavior. These results demonstrate that characterizing the deviation from the open-cell model is vital to gain a full understanding of scaffold biophysical properties, and provide a template for structural studies of other freeze-dried biomaterials. Freeze-dried collagen sponges are three-dimensional microporous scaffolds that have been used for a number of exploratory tissue engineering applications. The characterization of the structure-properties relationships of these scaffolds is

  4. Effect of repeated drying-wetting-freezing-thawing cycles on the active soil organic carbon pool

    NASA Astrophysics Data System (ADS)

    Semenov, V. M.; Kogut, B. M.; Lukin, S. M.

    2014-04-01

    Samples of soddy-podzolic soil (long-term overgrown fallow and continuous bare fallow), gray forest soil (forest, farming agrocenosis), and a typical chernozem (virgin steppe, forest area, farming agrocenosis, continuous bare fallow) have been incubated under stable conditions; other samples of these soils have been subjected to six drying-wetting-incubation-freezing-thawing-incubation cycles during 136 days. The wetting of dried soils and the thawing of frozen soils result in an abrupt but short increase in the emission rate of C-CO2 by 2.7-12.4 and 1.6-2.7 times, respectively, compared to the stable incubation conditions. As the soil is depleted in potentially mineralizable organic matter, the rate of the C-CO2 emission pulses initiated by disturbing impacts decreases. The cumulative extra production of C-CO2 by soils of natural lands for six cycles makes up 21-40% of that in the treatments with stable incubation conditions; the corresponding value for cultivated soils, including continuous clean fallow, is in the range of 45-82%. The content of potentially mineralizable organic matter in the soils subjected to recurrent drying-wetting-freezingthawing cycles decreased compared to the soils without disturbing impacts by 1.6-4.4 times, and the mineralization constants decreased by 1.9-3.6 times. It has been emphasized that the cumulative effect of drying-wetting-freezing-thawing cycles is manifested not only in the decrease in the total Corg from the soil but also in the reduction of the mineralization potential of the soil organic matter.

  5. Whey-cheese production using freeze-dried kefir culture as a starter.

    PubMed

    Dimitrellou, D; Kourkoutas, Y; Banat, I M; Marchant, R; Koutinas, A A

    2007-10-01

    The aim of the present study was to evaluate the use of a freeze-dried kefir culture in the production of a novel type of whey-cheese similar to traditional Greek Myzithra-cheese, to achieve improvement of the quality characteristics of the final product and the extension of shelf-life. The use of kefir culture as a starter led to increased lactic acid concentrations and decreased pH values in the final product compared with whey-cheese without starter culture. The effect of the starter culture on production of aroma-related compounds responsible for cheese flavour was also studied using the solid phase microextraction gas chromatography/mass spectrometry technique. Spoilage in unsalted kefir-whey-cheese was observed on the thirteenth and the twentieth day of preservation at 10 and 5 degrees C, respectively, while the corresponding times for unsalted whey-cheese preservation were 11 and 14 days. The cheeses produced were characterized as high-quality products during the preliminary sensory evaluation. An indication of increased preservation time was attributed to the freeze-dried kefir culture, which also seemed to suppress growth of pathogens. The results suggested the use of kefir culture as a means to extend the shelf-life of dairy products with reduced or no salt content.

  6. Microencapsulation of Natural Anthocyanin from Purple Rosella Calyces by Freeze Drying

    NASA Astrophysics Data System (ADS)

    Nafiunisa, A.; Aryanti, N.; Wardhani, D. H.; Kumoro, A. C.

    2017-11-01

    Anthocyanin extract in powder form will improve its use since the powder is easier to store and more applicable. Microencapsulation method is introduced as an efficient way for protecting pigment such as anthocyanin. This research was aimed to characterise anthocyanin encapsulated products prepared from purple Roselle calyces by freeze drying. The liquid anthocyanin extracts from ultrasound-assisted extraction were freeze-dried with and without the addition of 10% w/w maltodextrins as a carrier and coating agents. The quality attributes of the powders were characterised by their colour intensity, water content, and solubility. Analysis of encapsulated material was performed for the powder added by maltodextrin. The stability of the microencapsulated pigment in solution form was determined for 11 days. Total anthocyanin content was observed through pH differential method. The results of the colour intensity analysis confirm that the product with maltodextrin addition has more intense colour with L* value of 29.69 a* value of 54.29 and b* value of 8.39. The result with the addition of maltodextrin has less moisture content and more soluble in water. It is verified that better results were obtained for powder with maltodextrin addition. Anthocyanin in the powder form with maltodextrin addition exhibits higher stability even after 11 days. In conclusion, the microencapsulation of anthocyanin with maltodextrin as a carrier and coating agent presented a potential method to produce anthocyanin powder from purple Roselle.

  7. Development of a Freeze-Dried Fungal Wettable Powder Preparation Able to Biodegrade Chlorpyrifos on Vegetables

    PubMed Central

    Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

    2014-01-01

    Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues. PMID:25061758

  8. Development of a freeze-dried fungal wettable powder preparation able to biodegrade chlorpyrifos on vegetables.

    PubMed

    Liu, Jie; He, Yue; Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

    2014-01-01

    Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues.

  9. Quality by design: scale-up of freeze-drying cycles in pharmaceutical industry.

    PubMed

    Pisano, Roberto; Fissore, Davide; Barresi, Antonello A; Rastelli, Massimo

    2013-09-01

    This paper shows the application of mathematical modeling to scale-up a cycle developed with lab-scale equipment on two different production units. The above method is based on a simplified model of the process parameterized with experimentally determined heat and mass transfer coefficients. In this study, the overall heat transfer coefficient between product and shelf was determined by using the gravimetric procedure, while the dried product resistance to vapor flow was determined through the pressure rise test technique. Once model parameters were determined, the freeze-drying cycle of a parenteral product was developed via dynamic design space for a lab-scale unit. Then, mathematical modeling was used to scale-up the above cycle in the production equipment. In this way, appropriate values were determined for processing conditions, which allow the replication, in the industrial unit, of the product dynamics observed in the small scale freeze-dryer. This study also showed how inter-vial variability, as well as model parameter uncertainty, can be taken into account during scale-up calculations.

  10. On the Design of a Fuzzy Logic-Based Control System for Freeze-Drying Processes.

    PubMed

    Fissore, Davide

    2016-12-01

    This article is focused on the design of a fuzzy logic-based control system to optimize a drug freeze-drying process. The goal of the system is to keep product temperature as close as possible to the threshold value of the formulation being processed, without trespassing it, in such a way that product quality is not jeopardized and the sublimation flux is maximized. The method involves the measurement of product temperature and a set of rules that have been obtained through process simulation with the goal to obtain a unique set of rules for products with very different characteristics. Input variables are the difference between the temperature of the product and the threshold value, the difference between the temperature of the heating fluid and that of the product, and the rate of change of product temperature. The output variables are the variation of the temperature of the heating fluid and the pressure in the drying chamber. The effect of the starting value of the input variables and of the control interval has been investigated, thus resulting in the optimal configuration of the control system. Experimental investigation carried out in a pilot-scale freeze-dryer has been carried out to validate the proposed system. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Freeze-drying of HI-6-loaded recombinant human serum albumin nanoparticles for improved storage stability.

    PubMed

    Dadparvar, Miriam; Wagner, Sylvia; Wien, Sascha; Worek, Franz; von Briesen, Hagen; Kreuter, Jörg

    2014-10-01

    Severe intoxications with organophosphates require the immediate administration of atropine in combination with acetyl cholinesterase (AChE) reactivators such as HI-6. Although this therapy regimen enables the treatment of peripheral symptoms, the blood-brain barrier (BBB) restricts the access of the hydrophilic antidotes to the central nervous system which could lead to a fatal respiratory arrest. Therefore, HI-6-loaded albumin nanoparticles were previously developed to enhance the transport across this barrier and were able to reactivate organophosphate-(OP)-inhibited AChE in an in vitro BBB model. Since HI-6 is known to be moisture-sensitive, the feasibility of freeze-drying of the HI-6-loaded nanoparticles was investigated in the present study using different cryo- and lyoprotectants at different concentrations. Trehalose and sucrose (3%, w/v)-containing formulations were superior to mannitol concerning the physicochemical parameters of the nanoparticles whereas trehalose-containing samples were subject of a prolonged storage stability study at temperatures between -20°C and +40°C for predetermined time intervals. Shelf-life computations of the freeze-dried HI-6 nanoparticle formulations revealed a shelf-life time of 18 months when stored at -20°C. The formulations' efficacy was proven in vitro by reactivation of OP-inhibited AChE after transport over a porcine brain capillary endothelial cell layer model. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Simple Freeze-Drying Procedure for Producing Nanocellulose Aerogel-Containing, High-Performance Air Filters.

    PubMed

    Nemoto, Junji; Saito, Tsuguyuki; Isogai, Akira

    2015-09-09

    Simple freeze-drying of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibril (TOCN) dispersions in water/tert-butyl alcohol (TBA) mixtures was conducted to prepare TOCN aerogels as high-performance air filter components. The dispersibility of the TOCNs in the water/TBA mixtures, and the specific surface area (SSA) of the resulting TOCN aerogels, was investigated as a function of the TBA concentration in the mixtures. The TOCNs were homogeneously dispersed in the water/TBA mixtures at TBA concentrations up to 40% w/w. The SSAs of the TOCN aerogels exceeded 300 m2/g when the TBA concentration in the aqueous mixtures was in the range from 20% to 50% w/w. When a commercially available, high-efficiency particulate air (HEPA) filter was combined with TOCN/water/TBA dispersions prepared using 30% TBA, and the product was freeze-dried, the resulting TOCN aerogel-containing filters showed superior filtration properties. This was because nanoscale, spider-web-like networks of the TOCNs with large SSAs were formed within the filter.

  13. Non-enzymatic browning and flavour kinetics of vacuum dried onion slices

    NASA Astrophysics Data System (ADS)

    Mitra, Jayeeta; Shrivastava, Shanker L.; Rao, Pavuluri S.

    2015-01-01

    Onion slices were dehydrated under vacuum to produce good quality dried ready-to-use onion slices. Colour development due to non-enzymatic browning and flavour loss in terms of thiosulphinate concentration was determined, along with moisture content and rehydration ratio. Kinetics of non-enzymatic browning and thiosulphinate loss during drying was analysed. Colour change due to non-enzymatic browning was found to be much lower in the case of vacuum dried onion, and improved flavour retention was observed as compared to hot air dried onion slices. The optical index values for non-enzymatic browning varied from 18.41 to 38.68 for untreated onion slices and from 16.73 to 36.51 for treated slices, whereas thiosulphinate concentration in the case of untreated onion slices was within the range of 2.96-3.92 μmol g-1 for dried sample and 3.71-4.43 μmol g-1 for the treated onion slices. Rehydration ratio was also increased, which may be attributed to a better porous structure attained due to vacuum drying. The treatment applied was found very suitable in controlling non-enzymatic browning and flavour loss during drying, besides increasing rehydration ratio. Hence, high quality dried ready- to-use onion slices were prepared.

  14. Freeze-dried snake antivenoms formulated with sorbitol, sucrose or mannitol: comparison of their stability in an accelerated test.

    PubMed

    Herrera, María; Tattini, Virgilio; Pitombo, Ronaldo N M; Gutiérrez, José María; Borgognoni, Camila; Vega-Baudrit, José; Solera, Federico; Cerdas, Maykel; Segura, Alvaro; Villalta, Mauren; Vargas, Mariángela; León, Guillermo

    2014-11-01

    Freeze-drying is used to improve the long term stability of pharmaceutical proteins. Sugars and polyols have been successfully used in the stabilization of proteins. However, their use in the development of freeze-dried antivenoms has not been documented. In this work, whole IgG snake antivenom, purified from equine plasma, was formulated with different concentrations of sorbitol, sucrose or mannitol. The glass transition temperatures of frozen formulations, determined by Differential Scanning Calorimetry (DSC), ranged between -13.5 °C and -41 °C. In order to evaluate the effectiveness of the different stabilizers, the freeze-dried samples were subjected to an accelerated stability test at 40 ± 2 °C and 75 ± 5% relative humidity. After six months of storage at 40 °C, all the formulations presented the same residual humidity, but significant differences were observed in turbidity, reconstitution time and electrophoretic pattern. Moreover, all formulations, except antivenoms freeze-dried with mannitol, exhibited the same potency for the neutralization of lethal effect of Bothrops asper venom. The 5% (w:v) sucrose formulation exhibited the best stability among the samples tested, while mannitol and sorbitol formulations turned brown. These results suggest that sucrose is a better stabilizer than mannitol and sorbitol in the formulation of freeze-dried antivenoms under the studied conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Preservation of pathological tissue specimens by freeze-drying for immunohistochemical staining and various molecular biological analyses.

    PubMed

    Matsuo, S; Sugiyama, T; Okuyama, T; Yoshikawa, K; Honda, K; Takahashi, R; Maeda, S

    1999-05-01

    Conditions of preserving DNA, RNA and protein in pathological specimens are of great importance as degradation of such macromolecules would critically affect results of molecular biological analysis. The feasibility of freeze-drying as a means of preserving pathological tissue samples for molecular analysis has previously been shown. In the present study, further tests on long-term storage conditions and analyses of freeze-dried samples by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, western blotting and immunohistochemistry are reported. Rat chromosomal DNA of freeze-dried samples stored for 4 years showed slight degradation while RNA degradation was more prominently seen at an earlier stage of storage. However, these 4 year DNA and RNA samples were still able to serve as a template for some PCR and RT-PCR analyses, respectively. Overexpression of c-erbB-2 and p53 protein was demonstrated by western blotting and immunohistochemical staining using freeze-dried human breast cancer tissues. Although macromolecules in freeze-dried samples degrade to some extent during the preservation period, they should still be of value for certain molecular biological analyses and morphological examination; hence, providing more convenient and inexpensive ways of pathological tissue storage.

  16. NaCl stress impact on the key enzymes in glycolysis from Lactobacillus bulgaricus during freeze-drying.

    PubMed

    Li, Chun; Sun, Jinwei; Qi, Xiaoxi; Liu, Libo

    2015-01-01

    The viability of Lactobacillus bulgaricus in freeze-drying is of significant commercial interest to dairy industries. In the study, L.bulgaricus demonstrated a significantly improved (p < 0.05) survival rate during freeze-drying when subjected to a pre-stressed period under the conditions of 2% (w/v) NaCl for 2 h in the late growth phase. The main energy source for the life activity of lactic acid bacteria is related to the glycolytic pathway. To investigate the phenomenon of this stress-related viability improvement in L. bulgaricus, the activities and corresponding genes of key enzymes in glycolysis during 2% NaCl stress were studied. NaCl stress significantly enhanced (p < 0.05) glucose utilization. The activities of glycolytic enzymes (phosphofructokinase, pyruvate kinase, and lactate dehydrogenase) decreased during freeze-drying, and NaCl stress were found to improve activities of these enzymes before and after freeze-drying. However, a transcriptional analysis of the corresponding genes suggested that the effect of NaCl stress on the expression of the pfk2 gene was not obvious. The increased survival of freeze-dried cells of L. bulgaricus under NaCl stress might be due to changes in only the activity or translation level of these enzymes in different environmental conditions but have no relation to their mRNA transcription level.

  17. Microwave application on air drying of apple (var. Granny Smith). The influence of vacuum impregnation pretreatment

    NASA Astrophysics Data System (ADS)

    Martin Esparza, Maria Eugenia

    Combined hot air-microwave drying has been studied on apple (var. Granny Smith), with and without vacuum impregnation (VI) pretreatment with isotonic solution, respect to kinetics, microstructural and final quality items. In order to reach this objective, a drier has been designed and built, that allows to control and to register all the variables which take place during the drying process. Thermal and dielectric properties, that are very important characteristics when studying heat and mass transfer phenomena that occur during the combined drying process, have been related to temperature and/or moisture content throughout empirical equations. It could be observed that all these properties decreased with product moisture content. Respect to dielectric properties, a relationship among water binding forms to food structure and water molecules relaxation frequency has been found. On the other hand, the effect of drying treatment conditions (air rate, drying temperature, sample thickness and incident microwave power) on the drying rate, from an empirical model based on diffusional mechanisms with two kinetic parameters (k1 and k2), both function of the incident microwave power, has been studied. Microwave application to air drying implied a notable decrease on drying time, the higher the applied power the higher the reduction. Microstructural study by Cryo-Sem revealed fast water vaporization taking place when microwaves are applied. Vacuum impregnation did not implied an additional advantage for combined drying as drying rate was similar to that of NIV samples. Finally, it has been studied the influence of process conditions on the color and mechanical properties of the dried product (IV and NIV). Vacuum impregnation implied an increase on the fracture resistance and less purity and tone angle. Microwave application induced product browning with respect to air drying (tone decreased and purity increased).

  18. Modeling and optimization of red currants vacuum drying process by response surface methodology (RSM).

    PubMed

    Šumić, Zdravko; Vakula, Anita; Tepić, Aleksandra; Čakarević, Jelena; Vitas, Jasmina; Pavlić, Branimir

    2016-07-15

    Fresh red currants were dried by vacuum drying process under different drying conditions. Box-Behnken experimental design with response surface methodology was used for optimization of drying process in terms of physical (moisture content, water activity, total color change, firmness and rehydratation power) and chemical (total phenols, total flavonoids, monomeric anthocyanins and ascorbic acid content and antioxidant activity) properties of dried samples. Temperature (48-78 °C), pressure (30-330 mbar) and drying time (8-16 h) were investigated as independent variables. Experimental results were fitted to a second-order polynomial model where regression analysis and analysis of variance were used to determine model fitness and optimal drying conditions. The optimal conditions of simultaneously optimized responses were temperature of 70.2 °C, pressure of 39 mbar and drying time of 8 h. It could be concluded that vacuum drying provides samples with good physico-chemical properties, similar to lyophilized sample and better than conventionally dried sample. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

    PubMed Central

    Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

    2013-01-01

    Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

  20. The immunogenicity of thin-film freeze-dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures.

    PubMed

    Thakkar, Sachin G; Ruwona, Tinashe B; Williams, Robert O; Cui, Zhengrong

    2017-04-03

    Insoluble aluminum salts such as aluminum oxyhydroxide have been used for decades as adjuvants in human vaccines, and many vaccines contain aluminum salts as adjuvants. Aluminum salt-adjuvanted vaccines must be managed in cold-chain (2-8° C) during transport and storage, as vaccine antigens in general are too fragile to be stable in ambient temperatures, and unintentional slowing freezing causes irreversible aggregation and permanent damage to the vaccines. Previously, we reported that thin-film freeze-drying can be used to convert vaccines adjuvanted with an aluminum salt from liquid suspension into dry powder without causing particle aggregation or decreasing in immunogenicity following reconstitution. In the present study, using ovalbumin (OVA)-adsorbed Alhydrogel® (i.e. aluminum oxyhydroxide, 2% w/v) as a model vaccine, we showed that the immunogenicity of thin-film freeze-dried OVA-adsorbed Alhydrogel® vaccine powder was not significantly changed after it was exposed for an extended period of time in temperatures as high as 40° C or subjected to repeated slow freezing-and-thawing. It is expected that immunization programs can potentially benefit by integrating thin-film freeze-drying into vaccine preparations.

  1. The immunogenicity of thin-film freeze-dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures

    PubMed Central

    Thakkar, Sachin G.; Ruwona, Tinashe B.; Williams, Robert O.; Cui, Zhengrong

    2017-01-01

    ABSTRACT Insoluble aluminum salts such as aluminum oxyhydroxide have been used for decades as adjuvants in human vaccines, and many vaccines contain aluminum salts as adjuvants. Aluminum salt-adjuvanted vaccines must be managed in cold-chain (2–8° C) during transport and storage, as vaccine antigens in general are too fragile to be stable in ambient temperatures, and unintentional slowing freezing causes irreversible aggregation and permanent damage to the vaccines. Previously, we reported that thin-film freeze-drying can be used to convert vaccines adjuvanted with an aluminum salt from liquid suspension into dry powder without causing particle aggregation or decreasing in immunogenicity following reconstitution. In the present study, using ovalbumin (OVA)-adsorbed Alhydrogel® (i.e. aluminum oxyhydroxide, 2% w/v) as a model vaccine, we showed that the immunogenicity of thin-film freeze-dried OVA-adsorbed Alhydrogel® vaccine powder was not significantly changed after it was exposed for an extended period of time in temperatures as high as 40° C or subjected to repeated slow freezing-and-thawing. It is expected that immunization programs can potentially benefit by integrating thin-film freeze-drying into vaccine preparations. PMID:28051903

  2. Effect of cryoprotectants on the porosity and stability of insulin-loaded PLGA nanoparticles after freeze-drying

    PubMed Central

    Fonte, Pedro; Soares, Sandra; Costa, Ana; Andrade, José Carlos; Seabra, Vítor; Reis, Salette; Sarmento, Bruno

    2012-01-01

    PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability. PMID:23507897

  3. Porosity and water activity effects on stability of crystalline β-carotene in freeze-dried solids.

    PubMed

    Harnkarnsujarit, Nathdanai; Charoenrein, Sanguansri; Roos, Yrjö H

    2012-11-01

    Stability of entrapped crystalline β-carotene as affected by water activity, solids microstructure, and composition of freeze-dried systems was investigated. Aliquots (1000 mm(3) , 20% w/w solids) of solutions of maltodextrins of various dextrose equivalents (M040:DE6, M100:DE11, and M250:DE25.5), M100-sugars (1:1 glucose, fructose and sucrose), and agar for gelation with dispersed β-carotene were frozen at -20, -40, or -80 °C and freeze-dried. Glass transition and α-relaxation temperatures were determined with differential scanning calorimetry and dynamic mechanical analysis, respectively. β-Carotene contents were monitored spectrophotometrically. In the glassy solids, pore microstructure had a major effect on β-carotene stability. Small pores with thin walls and large surface area allowed β-carotene exposure to oxygen which led to a higher loss, whereas structural collapse enhanced stability of β-carotene by decreasing exposure to oxygen. As water plasticized matrices, an increase in molecular mobility in the matrix enhanced β-carotene degradation. Stability of dispersed β-carotene was highest at around 0.2 a(w) , but decreasing structural relaxation times above the glass transition correlated well with the rate of β-carotene degradation at higher a(w) . Microstructure, a(w) , and component mobility are important factors in the control of stability of β-carotene in freeze-dried solids. β-Carotene expresses various nutritional benefits; however, it is sensitive to oxygen and the degradation contributes to loss of nutritional values as well as product color. To increase stability of β-carotene in freeze-dried foods, the amount of oxygen penetration need to be limited. The modification of freeze-dried food structures, for example, porosity and structural collapse, components, and humidity effectively enhance the stability of dispersed β-carotene in freeze-dried solids. © 2012 Institute of Food Technologists®

  4. Vacuum mechatronics

    NASA Technical Reports Server (NTRS)

    Hackwood, Susan; Belinski, Steven E.; Beni, Gerardo

    1989-01-01

    The discipline of vacuum mechatronics is defined as the design and development of vacuum-compatible computer-controlled mechanisms for manipulating, sensing and testing in a vacuum environment. The importance of vacuum mechatronics is growing with an increased application of vacuum in space studies and in manufacturing for material processing, medicine, microelectronics, emission studies, lyophylisation, freeze drying and packaging. The quickly developing field of vacuum mechatronics will also be the driving force for the realization of an advanced era of totally enclosed clean manufacturing cells. High technology manufacturing has increasingly demanding requirements for precision manipulation, in situ process monitoring and contamination-free environments. To remove the contamination problems associated with human workers, the tendency in many manufacturing processes is to move towards total automation. This will become a requirement in the near future for e.g., microelectronics manufacturing. Automation in ultra-clean manufacturing environments is evolving into the concept of self-contained and fully enclosed manufacturing. A Self Contained Automated Robotic Factory (SCARF) is being developed as a flexible research facility for totally enclosed manufacturing. The construction and successful operation of a SCARF will provide a novel, flexible, self-contained, clean, vacuum manufacturing environment. SCARF also requires very high reliability and intelligent control. The trends in vacuum mechatronics and some of the key research issues are reviewed.

  5. Recent developments in high efficient freeze-drying of fruits and vegetables assisted by microwave: A review.

    PubMed

    Fan, Kai; Zhang, Min; Mujumdar, Arun S

    2018-01-10

    Microwave heating has been applied in the drying of high-value solids as it affords a number of advantages, including shorter drying time and better product quality. Freeze-drying at cryogenic temperature and extremely low pressure provides the advantage of high product quality, but at very high capital and operating costs due partly to very long drying time. Freeze-drying coupled with a microwave heat source speeds up the drying rate and yields good quality products provided the operating unit is designed and operated to achieve the potential for an absence of hot spot developments. This review is a survey of recent developments in the modeling and experimental results on microwave-assisted freeze-drying (MFD) over the past decade. Owing to the high costs involved, so far all applications are limited to small-scale operations for the drying of high-value foods such as fruits and vegetables. In order to promote industrial-scale applications for a broader range of products further research and development efforts are needed to offset the current limitations of the process. The needs and opportunities for future research and developments are outlined.

  6. Inhibition of Listeria monocytogenes in Hot Dogs by Surface Application of Freeze-Dried Bacteriocin-Containing Powders from Lactic Acid Bacteria.

    PubMed

    Ünlü, Gülhan; Nielsen, Barbara; Ionita, Claudia

    2016-06-01

    Six lactic acid bacteria (LAB) strains, Lactococcus lactis BFE 920, L. lactis subsp. lactis ATCC 11454, L. lactis subsp. cremoris ATCC 14365, Lactobacillus curvatus L442, Lact. curvatus LTH 1174, and Lact. bavaricus MN, were grown in cheddar cheese whey supplemented with complex nutrient sources. Cell-free culture supernatants were freeze-dried, and the resulting bacteriocin-containing powders were applied on the surface of hot dogs that were inoculated (~4 log cfu/hot dog) with a five-strain Listeria monocytogenes cocktail. Hot dogs were vacuum-sealed and stored at 4 °C for 4 weeks. L. monocytogenes was enumerated, using both tryptic soy agar (TSA) and oxford listeria agar (OXA), on day 0 and at 1, 2, 3, and 4 weeks of the refrigerated storage. In hot dogs containing only the L. monocytogenes inoculum, L. monocytogenes counts increased from 4 up to 7 log cfu/hot dog. All samples containing freeze-dried bacteriocin-containing powders exhibited significantly lowered (P < 0.05) L. monocytogenes populations on the surface of hot dogs throughout the 4-week study except for bavaricin MN powder. Bacterial counts on hot dogs packed without any powder were statistically equal on day 0 when enumerated on OXA. Freeze-dried bacteriocin-containing powders from Lact. curvatus L442 and L. lactis subsp. cremoris ATCC 14365 decreased L. monocytogenes populations on the surface of hot dogs by greater than 2 log cfu/hot dog throughout the 4-week study. For the powdered bacteriocin preparations from L. lactis BFE 920, L. lactis subsp. lactis ATCC 11454, and Lact. curvatus LTH 1174, L. monocytogenes populations were determined to be approximately 3-log cfu/hot dog after 4 weeks of storage.

  7. Optimized pulmonary gene transfection in mice by spray-freeze dried powder inhalation.

    PubMed

    Mohri, Kohta; Okuda, Tomoyuki; Mori, Asami; Danjo, Kazumi; Okamoto, Hirokazu

    2010-06-01

    Spray-freeze drying (SFD) is an attractive technique to prepare highly porous dry powders for inhalation. However, there have been few reports of its application to dry powder inhalers (DPIs). Therefore, in this study, we prepared dry plasmid DNA (pDNA) powders with different molecular ratios of chitosan to pDNA (N/P ratios) by SFD. All the pDNA powders were spherical and highly porous, with particles approximately 20-40microm in geometric diameter. The morphology changed little with the alteration of the N/P ratio. On electrophoresis, a band of linear pDNA was detected in the preparation without chitosan, suggesting the destabilization of pDNA through SFD. However, the addition of chitosan protected pDNA from destabilization. Moreover, the pDNA powders were evaluated for pulmonary gene transfection efficiency using an in vivo dual imaging technique for gene DPIs developed previously. Maximum gene expression was observed at 9-12h following pulmonary administration of the powders into mice. The powder with the N/P ratio of 10 had the highest gene transfection efficiency. A higher affinity of chitosan for pDNA and a smaller (approximately 100nm) pDNA/chitosan complex (N/Pf10) were found at pH 6.5 (in lung) than at pH 7.4 (in physiological conditions), suggesting that the effective compaction of pDNA by chitosan at the N/P ratio of 10 at pH 6.5 contributes to the gene transfection efficiency in the lung. These results suggest inhalable dry pDNA powders with chitosan prepared by SFD to be a suitable formulation for pulmonary gene therapy. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. How Vial Geometry Variability Influences Heat Transfer and Product Temperature During Freeze-Drying.

    PubMed

    Scutellà, Bernadette; Passot, Stéphanie; Bourlés, Erwan; Fonseca, Fernanda; Tréléa, Ioan Cristian

    2017-03-01

    Vial design features can play a significant role in heat transfer between the shelf and the product and, consequently, in the final quality of the freeze-dried product. Our objective was to investigate the impact of the variability of some geometrical dimensions of a set of tubing vials commonly used for pharmaceuticals production on the distribution of the vial heat transfer coefficients (K v ) and its potential consequence on product temperature. Sublimation tests were carried out using pure water and 8 combinations of chamber pressure (4-50 Pa) and shelf temperature (-40°C and 0°C) in 2 freeze-dryers. K v values were individually determined for 100 vials located in the center of the shelf. Vial bottom curvature depth and contact area between the vial and the shelf were carefully measured for 120 vials and these data were used to calculate K v distribution due to variability in vial geometry. At low pressures commonly used for sensitive products (below 10 Pa), the vial-shelf contact area appeared crucial for explaining K v heterogeneity and was found to generate, in our study, a product temperature distribution of approximately 2°C during sublimation. Our approach provides quantitative guidelines for defining vial geometry tolerance specifications and product temperature safety margins. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Prediction of the acoustic and bubble fields in insonified freeze-drying vials.

    PubMed

    Louisnard, O; Cogné, C; Labouret, S; Montes-Quiroz, W; Peczalski, R; Baillon, F; Espitalier, F

    2015-09-01

    The acoustic field and the location of cavitation bubble are computed in vials used for freeze-drying, insonified from the bottom by a vibrating plate. The calculations rely on a nonlinear model of sound propagation in a cavitating liquid [Louisnard, Ultrason. Sonochem., 19, (2012) 56-65]. Both the vibration amplitude and the liquid level in the vial are parametrically varied. For low liquid levels, a threshold amplitude is required to form a cavitation zone at the bottom of the vial. For increasing vibration amplitudes, the bubble field slightly thickens but remains at the vial bottom, and the acoustic field saturates, which cannot be captured by linear acoustics. On the other hand, increasing the liquid level may promote the formation of a secondary bubble structure near the glass wall, a few centimeters below the free liquid surface. These predictions suggest that rather complex acoustic fields and bubble structures can arise even in such small volumes. As the acoustic and bubble fields govern ice nucleation during the freezing step, the final crystal's size distribution in the frozen product may crucially depend on the liquid level in the vial. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Improving Heat Transfer at the Bottom of Vials for Consistent Freeze Drying with Unidirectional Structured Ice.

    PubMed

    Rosa, Mónica; Tiago, João M; Singh, Satish K; Geraldes, Vítor; Rodrigues, Miguel A

    2016-10-01

    The quality of lyophilized products is dependent of the ice structure formed during the freezing step. Herein, we evaluate the importance of the air gap at the bottom of lyophilization vials for consistent nucleation, ice structure, and cake appearance. The bottom of lyophilization vials was modified by attaching a rectified aluminum disc with an adhesive material. Freezing was studied for normal and converted vials, with different volumes of solution, varying initial solution temperature (from 5°C to 20°C) and shelf temperature (from -20°C to -40°C). The impact of the air gap on the overall heat transfer was interpreted with the assistance of a computational fluid dynamics model. Converted vials caused nucleation at the bottom and decreased the nucleation time up to one order of magnitude. The formation of ice crystals unidirectionally structured from bottom to top lead to a honeycomb-structured cake after lyophilization of a solution with 4% mannitol. The primary drying time was reduced by approximately 35%. Converted vials that were frozen radially instead of bottom-up showed similar improvements compared with normal vials but very poor cake quality. Overall, the curvature of the bottom of glass vials presents a considerable threat to consistency by delaying nucleation and causing radial ice growth. Rectifying the vials bottom with an adhesive material revealed to be a relatively simple alternative to overcome this inconsistency.

  11. Controlled crystallization of the lipophilic drug fenofibrate during freeze-drying: elucidation of the mechanism by in-line Raman spectroscopy.

    PubMed

    de Waard, Hans; De Beer, Thomas; Hinrichs, Wouter L J; Vervaet, Chris; Remon, Jean-Paul; Frijlink, Henderik W

    2010-12-01

    We developed a novel process, "controlled crystallization during freeze-drying" to produce drug nanocrystals of poorly water-soluble drugs. This process involves freeze-drying at a relatively high temperature of a drug and a matrix material from a mixture of tertiary butyl alcohol and water, resulting in drug nanocrystals incorporated in a matrix. The aim of this study was to elucidate the mechanisms that determine the size of the drug crystals. Fenofibrate was used as a model lipophilic drug. To monitor the crystallization during freeze-drying, a Raman probe was placed just above the sample in the freeze-dryer. These in-line Raman spectroscopy measurements clearly revealed when the different components crystallized during freeze-drying. The solvents crystallized only during the freezing step, while the solutes only crystallized after the temperature was increased, but before drying started. Although the solutes crystallized only after the freezing step, both the freezing rate and the shelf temperature were critical parameters that determined the final crystal size. At a higher freezing rate, smaller interstitial spaces containing the freeze-concentrated fraction were formed, resulting in smaller drug crystals (based on dissolution data). On the other hand, when the solutes crystallized at a lower shelf temperature, the degree of supersaturation is higher, resulting in a higher nucleation rate and consequently more and therefore smaller crystals. In conclusion, for the model drug fenofibrate, a high freezing rate and a relatively low crystallization temperature resulted in the smallest crystals and therefore the highest dissolution rate.

  12. Effect of Microwave Vacuum Drying on the Drying Characteristics, Color, Microstructure, and Antioxidant Activity of Green Coffee Beans.

    PubMed

    Dong, Wenjiang; Cheng, Ke; Hu, Rongsuo; Chu, Zhong; Zhao, Jianping; Long, Yuzhou

    2018-05-11

    The aim of this study is to investigate the effect of microwave vacuum drying (MVD) on the drying characteristics and quality attributes of green coffee beans. We specifically focused on the effective moisture diffusion coefficient ( D eff ), surface temperature, glass transition temperature ( T g ), water state, and microstructure. The kinetics of color changes during drying, total phenolic content (TPC), and antioxidant activity (DPPH, FRAP, and ABTS) were also characterized. Microwave power during MVD affected the porosity of coffee beans, their color, TPC, and antioxidant activity. The Allometric 1 model was the most suitable for simulating surface temperature rise kinetics. Thermal processing of green coffee beans resulted in increased b* , L* , Δ E , and TPC values, and greater antioxidant capacity. These findings may provide a theoretical reference for the technical improvement, mechanisms of flavor compound formation, and quality control of dried green coffee beans.

  13. Okara: A Nutritionally Valuable By-product Able to Stabilize Lactobacillus plantarum during Freeze-drying, Spray-drying, and Storage.

    PubMed

    Quintana, Gabriel; Gerbino, Esteban; Gómez-Zavaglia, Andrea

    2017-01-01

    Okara is a nutritionally valuable by-product produced in large quantities as result of soymilk elaboration. This work proposes its use as both culture and dehydration medium during freeze-drying, spray-drying, and storage of Lactobacillus plantarum CIDCA 83114. Whole and defatted okara were employed as culture media for L. plantarum CIDCA 83114. The growth kinetics were followed by plate counting and compared with those of bacteria grown in MRS broth (control). No significant differences in plate counting were observed in the three media. The fatty acid composition of bacteria grown in whole and defatted okara showed a noticeable increase in the unsaturated/saturated (U/S) fatty acid ratio, with regard to bacteria grown in MRS. This change was mainly due to the increase in polyunsaturated fatty acids, namely C18:2. For dehydration assays, cultures in the stationary phase were neutralized and freeze-dried (with or without the addition of 250 mM sucrose) or spray-dried. Bacteria were plate counted immediately after freeze-drying or spray-drying and during storage at 4°C for 90 days. Freeze-drying in whole okara conducted to the highest bacterial recovery. Regarding storage, spray-dried bacteria previously grown in whole and defatted okara showed higher plate counts than those grown in MRS. On the contrary, freeze-dried bacteria previously grown in all the three culture media were those with the lowest plate counts. The addition of sucrose to the dehydration media improved their recovery. The higher recovery of microorganisms grown in okara after freeze-drying and spray-drying processes and during storage was ascribed to both the presence of fiber and proteins in the dehydration media, and the increase in U/S fatty acids ratio in bacterial membranes. The obtained results support for the first time the use of okara as an innovative matrix to deliver L. plantarum . Considering that okara is an agro-waste obtained in large quantities, these results represent an

  14. Okara: A Nutritionally Valuable By-product Able to Stabilize Lactobacillus plantarum during Freeze-drying, Spray-drying, and Storage

    PubMed Central

    Quintana, Gabriel; Gerbino, Esteban; Gómez-Zavaglia, Andrea

    2017-01-01

    Okara is a nutritionally valuable by-product produced in large quantities as result of soymilk elaboration. This work proposes its use as both culture and dehydration medium during freeze-drying, spray-drying, and storage of Lactobacillus plantarum CIDCA 83114. Whole and defatted okara were employed as culture media for L. plantarum CIDCA 83114. The growth kinetics were followed by plate counting and compared with those of bacteria grown in MRS broth (control). No significant differences in plate counting were observed in the three media. The fatty acid composition of bacteria grown in whole and defatted okara showed a noticeable increase in the unsaturated/saturated (U/S) fatty acid ratio, with regard to bacteria grown in MRS. This change was mainly due to the increase in polyunsaturated fatty acids, namely C18:2. For dehydration assays, cultures in the stationary phase were neutralized and freeze-dried (with or without the addition of 250 mM sucrose) or spray-dried. Bacteria were plate counted immediately after freeze-drying or spray-drying and during storage at 4°C for 90 days. Freeze-drying in whole okara conducted to the highest bacterial recovery. Regarding storage, spray-dried bacteria previously grown in whole and defatted okara showed higher plate counts than those grown in MRS. On the contrary, freeze-dried bacteria previously grown in all the three culture media were those with the lowest plate counts. The addition of sucrose to the dehydration media improved their recovery. The higher recovery of microorganisms grown in okara after freeze-drying and spray-drying processes and during storage was ascribed to both the presence of fiber and proteins in the dehydration media, and the increase in U/S fatty acids ratio in bacterial membranes. The obtained results support for the first time the use of okara as an innovative matrix to deliver L. plantarum. Considering that okara is an agro-waste obtained in large quantities, these results represent an

  15. Potential of Near-Infrared Chemical Imaging as Process Analytical Technology Tool for Continuous Freeze-Drying.

    PubMed

    Brouckaert, Davinia; De Meyer, Laurens; Vanbillemont, Brecht; Van Bockstal, Pieter-Jan; Lammens, Joris; Mortier, Séverine; Corver, Jos; Vervaet, Chris; Nopens, Ingmar; De Beer, Thomas

    2018-04-03

    Near-infrared chemical imaging (NIR-CI) is an emerging tool for process monitoring because it combines the chemical selectivity of vibrational spectroscopy with spatial information. Whereas traditional near-infrared spectroscopy is an attractive technique for water content determination and solid-state investigation of lyophilized products, chemical imaging opens up possibilities for assessing the homogeneity of these critical quality attributes (CQAs) throughout the entire product. In this contribution, we aim to evaluate NIR-CI as a process analytical technology (PAT) tool for at-line inspection of continuously freeze-dried pharmaceutical unit doses based on spin freezing. The chemical images of freeze-dried mannitol samples were resolved via multivariate curve resolution, allowing us to visualize the distribution of mannitol solid forms throughout the entire cake. Second, a mannitol-sucrose formulation was lyophilized with variable drying times for inducing changes in water content. Analyzing the corresponding chemical images via principal component analysis, vial-to-vial variations as well as within-vial inhomogeneity in water content could be detected. Furthermore, a partial least-squares regression model was constructed for quantifying the water content in each pixel of the chemical images. It was hence concluded that NIR-CI is inherently a most promising PAT tool for continuously monitoring freeze-dried samples. Although some practicalities are still to be solved, this analytical technique could be applied in-line for CQA evaluation and for detecting the drying end point.

  16. Freeze drying-assisted synthesis of Pt@reduced graphene oxide nanocomposites as excellent hydrogen sensor

    NASA Astrophysics Data System (ADS)

    Lu, Xiaojing; Song, Xinjie; Gu, Cuiping; Ren, Haibo; Sun, Yufeng; Huang, Jiarui

    2018-05-01

    Quick and efficient detection of low concentrations of hydrogen remains a challenge because of the stability of hydrogen. A sensor based on reduced oxide graphene functionalized with Pt nanoparticles is successfully fabricated using a freeze-drying method followed by heat treatment. The structure and morphology of the Pt@rGO nanocomposites are well analyzed by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The as-prepared Pt@rGO nanocomposites show excellent hydrogen gas sensing properties at a low working temperature of 50 °C. The sensitivity toward 0.5% hydrogen is 8%. The response and recovery times of the sensor exposed to 0.5% hydrogen are 63 and 104 s, respectively. The gas-sensing mechanism of Pt@rGO sensor is also discussed.

  17. Influence of residual moisture and sealing atmosphere on viability of two freeze-dried viral vaccines.

    PubMed

    Precausta, P M; Simatos, D; Le Pemp, M; Devaux, B; Kato, F

    1980-10-01

    This study demonstrated the complexity of the factors leading to changes in the infectivity titers of freeze-dried canine distemper and poultry infectious bronchitis viral vaccines. The change in moisture content during the storage period was an additional parameter which may influence the infectivity titer. The results emphasized the difficulty of predetermining variations in infectivity titers from the initial residual moisture. The analysis of the variations in infectivity titers during the storage of two vaccines led to the formulation of a hypothesis of the presence of two components of different thermostability. Moreover, the temporary increase in the infectivity titer of infectious bronchitis vaccine stored progressively dissociating during storage concurrent with a progressive inactivation of infectious particles.

  18. Large scale synthesis of nanostructured zirconia-based compounds from freeze-dried precursors

    NASA Astrophysics Data System (ADS)

    Gómez, A.; Villanueva, R.; Vie, D.; Murcia-Mascaros, S.; Martínez, E.; Beltrán, A.; Sapiña, F.; Vicent, M.; Sánchez, E.

    2013-01-01

    Nanocrystalline zirconia powders have been obtained at the multigram scale by thermal decomposition of precursors resulting from the freeze-drying of aqueous acetic solutions. This technique has equally made possible to synthesize a variety of nanostructured yttria or scandia doped zirconia compositions. SEM images, as well as the analysis of the XRD patterns, show the nanoparticulated character of those solids obtained at low temperature, with typical particle size in the 10-15 nm range when prepared at 673 K. The presence of the monoclinic, the tetragonal or both phases depends on the temperature of the thermal treatment, the doping concentration and the nature of the dopant. In addition, Rietveld refinement of the XRD profiles of selected samples allows detecting the coexistence of the tetragonal and the cubic phases for high doping concentration and high thermal treatment temperatures. Raman experiments suggest the presence of both phases also at relatively low treatment temperatures.

  19. Unique organogel formation with macroporous materials constructed by the freeze-drying of aqueous cyclodextrin solutions.

    PubMed

    Marui, Yasuhiro; Kikuzawa, Akira; Kida, Toshiyuki; Akashi, Mitsuru

    2010-07-06

    Macroporous cyclodextrin materials (MP-alpha-, beta-, and gamma-CDs) were easily fabricated by the freeze-drying of aqueous solutions of alpha-, beta-, and gamma-CDs. These MP-CDs showed the absorption ability toward various organic solvents and oils to give organogels at ambient temperature. The morphological changes of the MP-CD microstructures were observed through the absorption of organic solvents. In particular, the absorption of polar organic solvents with hydrogen-bond forming ability, including 1,4-dioxane and ethanol, by the MP-CDs caused remarkable morphological changes in the microstructures. The absorption of these polar solvents by MP-alpha- and gamma-CDs resulted in the formation of channel-type assemblies of alpha- and gamma-CDs, respectively.

  20. The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems.

    PubMed

    Craig, D Q; Royall, P G; Kett, V L; Hopton, M L

    1999-03-15

    Many pharmaceuticals, either by accident or design, may exist in a total or partially amorphous state. Consequently, it is essential to have an understanding of the physico-chemical principles underpinning the behaviour of such systems. In this discussion, the nature of the glassy state will be described, with particular emphasis on the molecular processes associated with glass transitional behaviour and the use of thermal methods for characterising the glass transition temperature, Tg. The practicalities of such measurements, the significance of the accompanying relaxation endotherm and plasticization effects are considered. The advantages and difficulties associated with the use of amorphous drugs will be outlined, with discussion given regarding the problems associated with physical and chemical stability. Finally, the principles of freeze drying will be described, including discussion of the relevance of glass transitional behaviour to product stability. Copyright

  1. Controlled nucleation in freeze-drying: effects on pore size in the dried product layer, mass transfer resistance, and primary drying rate.

    PubMed

    Konstantinidis, Alex K; Kuu, Wei; Otten, Lori; Nail, Steven L; Sever, Robert R

    2011-08-01

    A novel and scalable method has been developed to enable control of the ice nucleation step for the freezing process during lyophilization. This method manipulates the chamber pressure of the freeze dryer to simultaneously induce nucleation in all product vials at a desired temperature. The effects of controlled nucleation on the drying rate of various formulations including 5% (w/w) mannitol, 5% (w/w) sucrose, and a mixture of 3% (w/w) mannitol and 2% (w/w) sucrose were studied. For a 5% (w/w) mannitol, uncontrolled ice nucleation occurred randomly at product temperatures between -8.0°C and -15.9°C as the vials were cooled to -40°C. Controlled ice nucleation was achieved at product temperatures between -2.3°C and -3.7°C. The effect of nucleation control on the effective pore radius (r(e) ) of the cake was determined from the product temperature profiles using a pore diffusion model in combination with a nonlinear parameter estimation approach reported earlier. Results show that the value of r(e) for 5% (w/w) mannitol was enlarged from 13 to 27 μm by uniformly inducing nucleation at higher temperatures. Applying the resistance parameters obtained from the pore diffusion model for 5% (w/w) mannitol, optimized cycles were theoretically generated and experimentally tested, resulting in a 41% reduction in primary drying time. Copyright © 2011 Wiley-Liss, Inc.

  2. Influence of vacuum drying temperature on: physico-chemical composition and antioxidant properties of murta berries

    Murta (Ugni molinae T.) berries were vacuum dried at a constant pressure of 15 kPa. The effects of processing temperatures (50, 60, 70, 80 and 90 °C) on the physico-chemical characteristics, the phenolic and flavonoid compounds, the antioxidant activity (measured by DPPH and ORAC) and the sugar and ...

  3. Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.

    PubMed

    Catalan-Latorre, Ana; Ravaghi, Maryam; Manca, Maria Letizia; Caddeo, Carla; Marongiu, Francesca; Ennas, Guido; Escribano-Ferrer, Elvira; Peris, José Esteban; Diez-Sales, Octavio; Fadda, Anna Maria; Manconi, Maria

    2016-10-01

    This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to increase their stability, led to a reduction of vesicle size and a good homogeneity of the systems, after simple rehydration with water. X-ray diffraction study demonstrated that after the freeze-drying process, curcumin remained successfully incorporated within the vesicles. All the vesicles displayed similar features: size ranging from 220 to 287nm, spherical or oval shape, multilamellar or large unilamellar morphology with a peculiar multicompartment organization involving 1-4 smaller vesicles inside. In vitro studies demonstrated the ability of the combined polymers to protect the vesicles from the harsh conditions of the gastro-intestinal tract (i.e., ionic strength and pH variation), which was confirmed in vivo by the greater deposition of curcumin in the intestinal region, as compared to the free drug in dispersion. This enhanced accumulation of curcumin provided by the eudragit-hyaluronan immobilized vesicles, together with an increase in Caco-2 cell viability exposed to hydrogen peroxide, indicated that vesicles can ensure a local protection against oxidative stress and an increase in its intestinal absorption. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Preparation and characterization of solid dispersion freeze-dried efavirenz - polyvinylpyrrolidone K-30.

    PubMed

    Fitriani, Lili; Haqi, Alianshar; Zaini, Erizal

    2016-01-01

    The aim of this research is to prepare and characterize solid dispersion of efavirenz - polyvinylpyrrolidone (PVP) K-30 by freeze drying to increase its solubility. Solid dispersion of efavirenz - PVP K-30 was prepared by solvent evaporation method with ratio 2:1, 1:1, and 1:2 and dried using a freeze dryer. Characterizations were done by scanning electron microscopy (SEM), powder X-ray diffraction analysis, differential thermal analysis (DTA), and Fourier transform infrared (FT-IR) spectroscopy. Solubility test was carried out in CO2-free distilled water, and efavirenz assay was conducted using high-performance liquid chromatography with acetonitrile:acetic acid (80:20) as the mobile phases. Powder X-ray diffractogram showed a decrease in the peak intensity, which indicated the crystalline altered to amorphous phase. DTA thermal analysis showed a decrease in the melting point of the solid dispersion compared to intact efavirenz. SEM results indicated the changes in the morphology of the crystal into an amorphous form compared to pure components. FT-IR spectroscopy analysis showed a shift wavenumber of the spectrum efavirenz and PVP K-30. The solubility of solid dispersion at ratio 2:1, 1:1, and 1:2 was 6.777 μg/mL, 6.936 μg/mL, and 14,672 μg/mL, respectively, whereas the solubility of intact efavirenz was 0.250 μg/mL. In conclusion, the solubility of solid dispersion increased significantly (P < 0.05).

  5. Freeze-dried, cross-linked bovine type I collagen: analysis of properties.

    PubMed

    Hyder, P R; Dowell, P; Singh, G; Dolby, A E

    1992-03-01

    This study was undertaken to assess the physical and biological properties of freeze-dried cross-linked bovine type I collagen and to assess its potential for use in the guided tissue regeneration method of treatment of periodontal disease in human adult subjects. The modulus of elasticity, swelling ratio, and biodegradation rate were investigated. The collagen sponge was implanted subdermally into Sprague-Dawley rats and a histological study carried out at 2, 7, 21, 35, and 49 days post implantation. Growth of human gingival and periodontal ligament derived fibroblasts on collagen sponge was assessed, as well as the effect of bovine collagen supernatants upon gingival and periodontal fibroblast cultures. The physical properties of the collagen sponge were consistent with good handling qualities and, therefore, it was appropriate for use at a surgical site. The histological study demonstrated a reduction in thickness of the collagen at 21 days; at 35 days there was a hazy appearance of the collagen remnants; and at 49 days the graft material had been completely replaced with fibrous tissues. The in vitro response of human gingival and periodontal fibroblasts to bovine collagen showed that, after 21 days, confluent fibroblast growth was observed around and underneath the sponge. The effect of bovine collagen supernatants upon fibroblasts demonstrated an apparent proliferative effect of the supernatant with both gingival and periodontal ligament fibroblasts. However, the non-parametric Friedman test revealed no significant differences between dilutions or time points. The overall findings provide encouraging evidence of the safety of freeze-dried cross-linked bovine collagen sponge in the surgical treatment of periodontal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Investigation of drying stresses on proteins during lyophilization: differentiation between primary and secondary-drying stresses on lactate dehydrogenase using a humidity controlled mini freeze-dryer.

    PubMed

    Luthra, Sumit; Obert, Jean-Philippe; Kalonia, Devendra S; Pikal, Michael J

    2007-01-01

    This article describes the design, performance testing, and application of a controlled humidity mini-freeze-dryer in studying the physical stability of lactate dehydrogenase during lyophilization. Performance evaluation of the mini-freeze-dryer was conducted with tests, namely water sublimation, radiation heat exchange, lowest achievable temperature, and leak testing. Protein stability studies were conducted by comparing protein activity at various stages of lyophilization with the initial activity. The shelf and condenser temperature were stable at <-40 degrees C, wall temperature was within 2 degrees C of the shelf temperature, and the leak rate was small. The chamber pressure was controlled by the ice on the condenser and the product temperature during sublimation was equal to the shelf temperature. Addition of Tween 80 prevented activity loss in solution and after freeze-thaw. No activity loss was observed after primary-drying even in absence of lyoprotectants and with collapse of cake structure. Five percent (w/w) sucrose concentration was required to achieve full stabilization. In conclusion, performance testing established that the mini-freeze-dryer was suitable for mechanistic freeze-drying studies. Secondary-drying was the critical step for protein stability. The concentration of sucrose required to stabilize the protein completely was several orders of magnitude higher than that required to satisfy the direct interaction requirement of the protein. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

  7. Effect of low-temperature preservation on the quality of vacuum-packaged dry-cured ham: Refrigerated boneless ham and frozen ham cuts.

    PubMed

    Cilla, Irene; Martínez, Luis; Beltrán, José Antonio; Roncalés, Pedro

    2006-05-01

    The effect of storage on dry-cured ham quality was studied. Sixteen vacuum-packaged boneless dry-cured hams and sixteen vacuum-packaged dry-cured ham cuts were stored in darkness under refrigeration (4±2°C; 8 months) or freezing (-18±1°C; 24 months), respectively. Instrumental colour and texture, physico-chemical and biochemical parameters, sensory profile and consumer acceptability and purchase satisfaction were measured throughout storage. The overall quality of refrigerated boneless dry-cured hams and frozen dry-cured ham cuts showed only limited changes throughout long-term storage. Significant changes involved loss of odour and flavour, increased adhesiveness and modification of hardness, the Semimembranosus muscle became tender while Biceps femoris became harder, leading to a higher textural homogeneity. In agreement with those changes, the overall acceptability assessed by a trained panel decreased throughout storage, though this was significant regarding only frozen hams. However, consumer evaluation of acceptability, as well as satisfaction with hypothetical purchasing, did not vary significantly throughout storage.

  8. Drying based on temperature-detection-assisted control in microwave-assisted pulse-spouted vacuum drying.

    PubMed

    Cao, Xiaohuang; Zhang, Min; Qian, He; Mujumdar, Arun S

    2017-06-01

    An online temperature-detection-assisted control system of microwave-assisted pulse-spouted vacuum drying was newly developed. By using this system, temperature control can be automatically and continuously adjusted based on the detection of drying temperature and preset temperature. Various strategies for constant temperature control, linear temperature control and three-step temperature control were applied to drying carrot cubes. Drying kinetics and the quality of various temperature-controlled strategies online are evaluated for the new drying technology as well as its suitability as an alternative drying method. Drying time in 70 °C mode 1 had the shortest drying time and lowest energy consumption in all modes. A suitable colour, highest re-hydration ratio and fracture-hardness, and longest drying time occurred in 30-40-50 °C mode 3. The number of hot spots was reduced in 40-50-60 °C mode 3. Acceptable carrot snacks were obtained in 50-60-70 °C mode 3 and 70 °C mode 2. All temperature curves showed that the actual temperatures followed the preset temperatures appropriately. With this system, a linear temperature-controlled strategy and a three-step temperature-controlled strategy can improve product quality and heating non-uniformity compared to constant temperature control, but need greater energy consumption and longer drying time. A temperature-detection-assisted control system was developed for providing various drying strategies as a suitable alternative in making a snack product. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  9. Structure influence on mechanical and acoustic properties of freeze-dried gels obtained with the use of hydrocolloids.

    PubMed

    Ciurzyńska, Agnieszka; Marzec, Agata; Mieszkowska, Arleta; Lenart, Andrzej

    2017-04-01

    The influence of the structure formed by the type of hydrocolloids (low-methoxyl pectin, the mixture of xanthan gum, and locust bean gum, and mixture of xanthan gum, and guar gum) and the aeration time (3, 5, 7, and 9 min) on textural properties of freeze-dried gels were investigated. The hardest texture generating the strongest acoustic emission was obtained by freeze-dried pectin gel, characterised by the lowest porosity and the largest pore diameter. Aeration time significantly affected mechanical and acoustic properties of the pectin gel lyophilisate. No effect of gel aeration time on tested characteristics of samples with mixture of hydrocolloids was observed. Strong positive correlations between acoustic energy as well as the maximum force and work and negative ones between porosity and pore diameter indicate that greater resilience and stronger acoustic emission of freeze-dried gels was caused by the reduction of porosity and the increase in the pore size of the material. The research is expected to show the phenomenon of structure formation when preparing and freeze-drying gels and explain the influence of the process parameters (time of aeration, the type of hydrocolloids) on the formation of the internal structure and physical properties of a dried product, especially mechanical and acoustic properties. This achievement will contribute to the development of the science of food and human nutrition, especially within the context of the popular research on aerated diet products. The expected result will be the ability to develop a new technology for producing food with a delicate texture, using the phenomenon of sublimation. As a result, designing changes in the structure of freeze-dried fruit gels with a delicate structure will be possible due to the choice of ingredients and aeration parameters in order to develop innovative food characterised by favorable nutritional, health and functional properties, which will be attractive for the consumers. © 2016

  10. Freeze-drying of “pearl milk tea”: A general strategy for controllable synthesis of porous materials

    PubMed Central

    Zhou, Yingke; Tian, Xiaohui; Wang, Pengcheng; Hu, Min; Du, Guodong

    2016-01-01

    Porous materials have been widely used in many fields, but the large-scale synthesis of materials with controlled pore sizes, pore volumes, and wall thicknesses remains a considerable challenge. Thus, the controllable synthesis of porous materials is of key general importance. Herein, we demonstrate the “pearl milk tea” freeze-drying method to form porous materials with controllable pore characteristics, which is realized by rapidly freezing the uniformly distributed template-containing precursor solution, followed by freeze-drying and suitable calcination. This general and convenient method has been successfully applied to synthesize various porous phosphate and oxide materials using different templates. The method is promising for the development of tunable porous materials for numerous applications of energy, environment, and catalysis, etc. PMID:27193866

  11. Evaluation of 3D-Printed Polycaprolactone Scaffolds Coated with Freeze-Dried Platelet-Rich Plasma for Bone Regeneration.

    PubMed

    Li, Junda; Chen, Meilin; Wei, Xiaoying; Hao, Yishan; Wang, Jinming

    2017-07-19

    Three-dimensional printing is one of the most promising techniques for the manufacturing of scaffolds for bone tissue engineering. However, a pure scaffold is limited by its biological properties. Platelet-rich plasma (PRP) has been shown to have the potential to improve the osteogenic effect. In this study, we improved the biological properties of scaffolds by coating 3D-printed polycaprolactone (PCL) scaffolds with freeze-dried and traditionally prepared PRP, and we evaluated these scaffolds through in vitro and in vivo experiments. In vitro, we evaluated the interaction between dental pulp stem cells (DPSCs) and the scaffolds by measuring cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation. The results showed that freeze-dried PRP significantly enhanced ALP activity and the mRNA expression levels of osteogenic genes (ALP, RUNX2 (runt-related gene-2), OCN (osteocalcin), OPN (osteopontin)) of DPSCs ( p < 0.05). In vivo, 5 mm calvarial defects were created, and the PRP-PCL scaffolds were implanted. The data showed that compared with traditional PRP-PCL scaffolds or bare PCL scaffolds, the freeze-dried PRP-PCL scaffolds induced significantly greater bone formation ( p < 0.05). All these data suggest that coating 3D-printed PCL scaffolds with freeze-dried PRP can promote greater osteogenic differentiation of DPSCs and induce more bone formation, which may have great potential in future clinical applications.

  12. Freeze-dried stallion spermatozoa: evaluation of two chelating agents and comparative analysis of three sperm DNA damage assays.

    PubMed

    Olaciregui, M; Luño, V; Martí, J I; Aramayona, J; Gil, L

    2016-11-01

    During the freeze-drying procedure, sperm DNA might become damaged by both freezing and drying stresses. Sperm DNA status can be detected using well-established assays; however, most techniques are expensive and involve elaborate protocols and equipment. Indirect assessments can provide alternative strategies. The objective of this study was to compare a simple test of DNA status using Diff-Quik (DQ) with two established procedures: acridine orange test (AOT) and sperm chromatin dispersion (SCD) on freeze-dried (FD) stallion spermatozoa. Ejaculated spermatozoa from three stallions were freeze-dried in basic medium supplemented with two different chelating agents: EGTA or EDTA. After rehydration, the spermatozoa were subjected to DNA damage detection using a SCDt, AOT and DQ stain simultaneously. The results showed that the DNA damage levels in the EGTA group were significantly lower than those in the EDTA group. AOT detected a significantly higher proportion of spermatozoa with fragmented DNA than DQ and SCD. The results of the SCD test and DQ stain exhibited a significant positive correlation for DNA fragmentation (r = 0.528), whereas a negative correlation was observed between SCD, DQ and AOT (r = -0.134 and r = -0.332 respectively). The present study shows that both the SCD test and DQ assay are effective methods for detecting FD stallion sperm DNA fragmentation, whereas using of AOT is questionable. © 2016 Blackwell Verlag GmbH.

  13. In Vitro Impact of Conditioned Medium From Demineralized Freeze-Dried Bone on Human Umbilical Endothelial Cells.

    PubMed

    Harnik, Branko; Miron, Richard J; Buser, Daniel; Gruber, Reinhard

    2017-03-01

    Angiogenesis is essential for the consolidation of bone allografts. The underlying molecular mechanism, however, remains unclear. Soluble factors released from demineralized freeze-dried bone target mesenchymal cells; however, their effect on endothelial cells has not been investigated so far. The aim of the present study was therefore to examine the effect of conditioned medium from demineralized freeze-dried bone on human umbilical endothelial cells in vitro. Conditioned medium was first prepared from demineralized freeze-dried bone following 24 hours incubation at room temperature to produce demineralized bone conditioned media. Thereafter, conditioned medium was used to stimulate human umbilical vein endothelial cells in vitro by determining the cell response based on viability, proliferation, expression of apoptotic genes, a Boyden chamber to determine cell migration, and the formation of branches. The authors report here that conditioned medium decreased viability and proliferation of endothelial cells. Neither of the apoptotic marker genes was significantly altered when endothelial cells were exposed to conditioned medium. The Boyden chamber revealed that endothelial cells migrate toward conditioned medium. Moreover, conditioned medium moderately stimulated the formation of branches. These findings support the concept that conditioned medium from demineralized freeze-dried bone targets endothelial cells by decreasing their proliferation and enhancing their motility under these in vitro conditions.

  14. Optimization of a cryoprotective medium to increase the viability of freeze-dried Streptococcus thermophilus by response surface methodology

    Streptococcus thermophilus normally exhibits different survival rates in different bacteria medium during freeze-drying. In this study, response surface methodology (RSM) was applied on the design of experiments for optimizing the cryoprotective medium. Results showed that the most significant facto...

  15. SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia coli and Salmonella typhimurium.

    PubMed

    Rosen, Rachel; Buchinger, Sebastian; Pfänder, Ramona; Pedhazur, Rami; Reifferscheid, Georg; Belkin, Shimshon

    2016-11-01

    We report the results of a study of the potential negative effects of the freeze-drying process, normally considered a benign means for long-term conservation of living cells and the golden standard in bacterial preservation. By monitoring gene induction using a whole-cell Escherichia coli bioreporter panel, in which diverse stress-responsive gene promoters are fused to luminescent or fluorescent reporting systems, we have demonstrated that DNA repair genes belonging to the SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation from the freeze-dried state, whereas other stress-responsive promoters such as grpE, katG, phoA, soxS, and sodA were not affected. This observation was confirmed by the UMU-chromotest (activation of the umuD gene promoter) in Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli SOS genes. We further show that a functional SOS operon is important in viability maintenance following resuscitation, but that at the same time, this repair system may introduce significantly higher mutation rates, comparable to those induced by high concentrations of a known mutagen. Our results also indicate that the entire freeze-drying process, rather than either freezing or drying separately, is instrumental in the induction of DNA damage.

  16. Particle characterization of poorly water-soluble drugs using a spray freeze drying technique.

    PubMed

    Kondo, Masahiro; Niwa, Toshiyuki; Okamoto, Hirokazu; Danjo, Kazumi

    2009-07-01

    A spray freeze drying (SFD) method was developed to prepare the composite particles of poorly water-soluble drug. The aqueous solution dissolved drug and the functional polymer was sprayed directly into liquid nitrogen. Then, the iced droplets were lyophilized with freeze-dryer to prepare solid particles. Tolbutamide (TBM) and hydroxypropylmethylcellulose (HPMC) were used as a model drug and water-soluble polymeric carrier in this study, respectively. The morphological observation of particles revealed that the spherical particles having porous structure could be obtained by optimizing the loading amount of drug and polymer in the spray solution. Especially, SFD method was characterized that the prepared particles had significantly larger specific surface area comparing with those prepared by the standard spray drying technique. The physicochemical properties of the resultant particles were found to be dependent on the concentration of spray solution. When the solution with high content of drug and polymer was used, the particle size of the resulting composite particles increased and they became spherical. The specific surface area of the particles also increased as a result of higher concentration of solution. The evaluation of spray solution indicated that these results were dependent on the viscosity of spray solution. In addition, when composite particles of TBM were prepared using the SFD method with HPMC as a carrier, the crystallinity of TBM decreased as the proportion of HPMC increased. When the TBM : HPMC ratio reached 1 : 5, the crystallinity of the particles completely disappeared. The dissolution tests showed that the release profiles of poorly water-soluble TBM from SFD composite particles were drastically improved compared to bulk TBM. The 70% release time T(70) of composite particles prepared by the SFD method in a solution of pH 1.2 was quite smaller than that of bulk TBM, while in a solution of pH 6.8, it was slightly lower. In addition, the

  17. Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations.

    PubMed

    Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

    2015-11-01

    We studied the stability of freeze-dried therapeutic protein formulations over a range of initial concentrations (from 40 to 160 mg/mL) and employed a variety of formulation strategies (including buffer-free freeze dried formulations, or BF-FDF). Highly concentrated, buffer-free liquid formulations of therapeutic monoclonal antibodies (mAbs) have been shown to be a viable alternative to conventionally buffered preparations. We considered whether it is feasible to use the buffer-free strategy in freeze-dried formulations, as an answer to some of the known drawbacks of conventional buffers. We therefore conducted an accelerated stability study (24 weeks at 40 °C) to assess the feasibility of stabilizing freeze-dried formulations without "classical" buffer components. Factors monitored included pH stability, protein integrity, and protein aggregation. Because the protein solutions are inherently self-buffering, and the system's buffer capacity scales with protein concentration, we included highly concentrated buffer-free freeze-dried formulations in the study. The tested formulations ranged from "fully formulated" (containing both conventional buffer and disaccharide stabilizers) to "buffer-free" (including formulations with only disaccharide lyoprotectant stabilizers) to "excipient-free" (with neither added buffers nor stabilizers). We evaluated the impacts of varying concentrations, buffering schemes, pHs, and lyoprotectant additives. At the end of 24 weeks, no change in pH was observed in any of the buffer-free formulations. Unbuffered formulations were found to have shorter reconstitution times and lower opalescence than buffered formulations. Protein stability was assessed by visual inspection, sub-visible particle analysis, protein monomer content, charge variants analysis, and hydrophobic interaction chromatography. All of these measures found the stability of buffer-free formulations that included a disaccharide stabilizer comparable to buffer

  18. Ultrasonic Spray Drying vs High Vacuum and Microwaves Technology for Blueberries

    NASA Astrophysics Data System (ADS)

    Candia-Muñoz, N.; Ramirez-Bunster, M.; Vargas-Hernández, Y.; Gaete-Garretón, L.

    Interest in high quality foods: good taste and a high content of nutrients with healthy beneficial effects are increasing. Fruits have good properties but, they are lost because the oxidation process, additionally, for different reasons a 40% of harvested fruit are lost. To conserve the fruit properties an ultrasonic assisted spray dryer was developed and tested, comparing its results with microwave-vacuum drying technology. Results did shown taste, color, smell, particle shape and size distribution better than the conventional one. The antioxidants conservation were quite good except in the anthocyanins, in which the microwave and vacuum technology shown best results.

  19. The effect of freezing and drying on leaching of DOM from above ground vascular plant material from the Alaskan Arctic

    NASA Astrophysics Data System (ADS)

    Khosh, M. S.; McClelland, J. W.

    2014-12-01

    Our understanding of the seasonal dynamics of fluvial dissolved organic matter (DOM) concentrations and fluxes in Arctic catchments has increased substantially during recent years, especially during the spring, which historically has been an under-sampled time period. While a number of studies have observed peaks in both DOM concentrations and fluxes during the spring snowmelt, our knowledge of the mechanisms that control these observations are still lacking. During the initial snowmelt period, frozen ground and the snow matrix act to constrain melt-water to the soil surface. We hypothesize that restriction of flow during this time facilitates leaching of DOM from senescent above ground vegetation and detritus contributing to the high DOM concentrations observed during the spring melt. This study focuses on the effect of freezing and drying on the leaching of dissolved organic carbon and nitrogen (DOC and DON) from above ground vascular plant material. Specifically, we examined the treatment effects of freezing, drying, and freeze-drying on three genera of common Alaskan Arctic vascular plants; Eriophorum (spp.), Carex (spp.), and Salix (spp.). Frozen and freeze-dried plant material released more DOC over the experimental 96 hour leaching period compared to plant material that was only dried. Qualitatively, these patterns were similar among the different plant types, while quantitatively Salix leached more DOC than either Eriophorum or Carex in all treatments. Similar patterns were also seen for DON between the different treatments and among the different plant types. Compositionally, DOM that was leached from frozen and freeze-dried material had higher C:N ratios than material that was only dried. Comparatively, DOM leached from Salix had much higher C:N ratios than either Eriophorum or Carex. During the first 24 hours of leaching, C:N ratios tended to increase followed by a subsequent leveling or decrease, suggesting that the composition of leached DOM varied

  20. Controlled ice nucleation using freeze-dried Pseudomonas syringae encapsulated in alginate beads.

    PubMed

    Weng, Lindong; Tessier, Shannon N; Swei, Anisa; Stott, Shannon L; Toner, Mehmet

    2017-04-01

    The control of ice nucleation is of fundamental significance in many process technologies related to food and pharmaceutical science and cryobiology. Mechanical perturbation, electromagnetic fields and ice-nucleating agents (INAs) have been known to induce ice nucleation in a controlled manner. But these ice-nucleating methods may suffer from cumbersome manual operations, safety concerns of external fields, and biocompatibility and recovery issues of INA particles, especially when used in living systems. Given the automatic ice-seeding nature of INAs, a promising solution to overcome some of the above limitations is to engineer a biocomposite that accommodates the INA particles but minimizes their interactions with biologics, as well as enabling the recovery of used particles. In this study, freeze-dried Pseudomonas syringae, a model ice-nucleating agent, was encapsulated into microliter-sized alginate beads. We evaluated the performance of the bacterial hydrogel beads to initiate ice nucleation in water and aqueous glycerol solution by investigating factors including the size and number of the beads and the local concentration of INA particles. In the aqueous sample of a fixed volume, the total mass of the INA particles (m) was found to be the governing parameter that is solely responsible for determining the ice nucleation performance of the bacterial hydrogel beads. The freezing temperature has a strong positive linear correlation with log 10 m. The findings in this study provide an effective, predictable approach to control ice nucleation, which can improve the outcome and standardization of many ice-assisted process technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Changes of hydrogen peroxide and radical-scavenging activity of raspberry during osmotic, convective, and freeze-drying.

    PubMed

    Novaković, Miroslav M; Stevanović, Snežana M; Gorjanović, Stanislava Ž; Jovanovic, Predrag M; Tešević, Vele V; Janković, Miodrag A; Sužnjević, Desanka Ž

    2011-05-01

    This study was conducted to investigate the influence of different drying treatments on antioxidant (AO) activity and phenolic content of raspberry (Rubus idaeus), cultivar Willamette. Whole raspberry fruits were dried convectively (air-drying), osmotically, and freeze-dried. Acetone-water extracts of fresh and dried raspberries were assessed for total phenolic content by standard Folin-Ciocalteau method. Two AO assays were applied, a recently developed direct current (DC) polarographic assay based on decrease of anodic oxidation current of hydrogen peroxide and widely used radical scavenge against the 1,1-diphenyl-2-picrylhydrazyl (DPPH). Strong correlation has been obtained between both AO assays and total phenolic content. In addition, some individual phenolic compounds present in raspberry have been assessed using DPPH and DC polarographic assay. Comparison and evaluation of drying methods has been based on preservation of AO activity and total phenolic content. Obtained results confirmed superiority of freeze-drying; convective drying caused slight changes while osmotic dehydration showed a significant decrease of phenolic compounds and AO activity. © 2011 Institute of Food Technologists®

  2. Effect of freeze-dryer design on drying rate of an amorphous protein-formulation determined with a gravimetric technique.

    PubMed

    Gieseler, Henning; Lee, Geoffrey

    2008-01-01

    A freeze-drying balance was used to determine momentary drying-rate, m(t), of a sucrose/BSA formulation contained in a vial with varying shelf packing density, Ø2. A comparison between two different laboratory-scale freeze-dryers was made. The effects of Ø2 on m(t) differed between the two units, attributed to drying chamber design and its effects on heat transfer. At high Ø2 the differences are annulled because of the shielding effects of surrounding vials. Parallel effects of Ø2 were also found on product temperature, Tb, measured in the balance vial. Tb was used to calculate vial heat transfer coefficient, Kv. Kv was strongly reduced with increasing Ø2, but reached a plateau value at high Ø2.

  3. Detecting phase separation of freeze-dried binary amorphous systems using pair-wise distribution function and multivariate data analysis.

    PubMed

    Chieng, Norman; Trnka, Hjalte; Boetker, Johan; Pikal, Michael; Rantanen, Jukka; Grohganz, Holger

    2013-09-15

    The purpose of this study is to investigate the use of multivariate data analysis for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to detect phase separation in freeze-dried binary amorphous systems. Polymer-polymer and polymer-sugar binary systems at various ratios were freeze-dried. All samples were analyzed by PXRD, transformed to PDF and analyzed by principal component analysis (PCA). These results were validated by differential scanning calorimetry (DSC) through characterization of glass transition of the maximally freeze-concentrate solute (Tg'). Analysis of PXRD-PDF data using PCA provides a more clear 'miscible' or 'phase separated' interpretation through the distribution pattern of samples on a score plot presentation compared to residual plot method. In a phase separated system, samples were found to be evenly distributed around the theoretical PDF profile. For systems that were miscible, a clear deviation of samples away from the theoretical PDF profile was observed. Moreover, PCA analysis allows simultaneous analysis of replicate samples. Comparatively, the phase behavior analysis from PXRD-PDF-PCA method was in agreement with the DSC results. Overall, the combined PXRD-PDF-PCA approach improves the clarity of the PXRD-PDF results and can be used as an alternative explorative data analytical tool in detecting phase separation in freeze-dried binary amorphous systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Optimization of a pharmaceutical freeze-dried product and its process using an experimental design approach and innovative process analyzers.

    PubMed

    De Beer, T R M; Wiggenhorn, M; Hawe, A; Kasper, J C; Almeida, A; Quinten, T; Friess, W; Winter, G; Vervaet, C; Remon, J P

    2011-02-15

    The aim of the present study was to examine the possibilities/advantages of using recently introduced in-line spectroscopic process analyzers (Raman, NIR and plasma emission spectroscopy), within well-designed experiments, for the optimization of a pharmaceutical formulation and its freeze-drying process. The formulation under investigation was a mannitol (crystalline bulking agent)-sucrose (lyo- and cryoprotector) excipient system. The effects of two formulation variables (mannitol/sucrose ratio and amount of NaCl) and three process variables (freezing rate, annealing temperature and secondary drying temperature) upon several critical process and product responses (onset and duration of ice crystallization, onset and duration of mannitol crystallization, duration of primary drying, residual moisture content and amount of mannitol hemi-hydrate in end product) were examined using a design of experiments (DOE) methodology. A 2-level fractional factorial design (2(5-1)=16 experiments+3 center points=19 experiments) was employed. All experiments were monitored in-line using Raman, NIR and plasma emission spectroscopy, which supply continuous process and product information during freeze-drying. Off-line X-ray powder diffraction analysis and Karl-Fisher titration were performed to determine the morphology and residual moisture content of the end product, respectively. In first instance, the results showed that - besides the previous described findings in De Beer et al., Anal. Chem. 81 (2009) 7639-7649 - Raman and NIR spectroscopy are able to monitor the product behavior throughout the complete annealing step during freeze-drying. The DOE approach allowed predicting the optimum combination of process and formulation parameters leading to the desired responses. Applying a mannitol/sucrose ratio of 4, without adding NaCl and processing the formulation without an annealing step, using a freezing rate of 0.9°C/min and a secondary drying temperature of 40°C resulted in

  5. Implementation of a process analytical technology system in a freeze-drying process using Raman spectroscopy for in-line process monitoring.

    PubMed

    De Beer, T R M; Allesø, M; Goethals, F; Coppens, A; Heyden, Y Vander; De Diego, H Lopez; Rantanen, J; Verpoort, F; Vervaet, C; Remon, J P; Baeyens, W R G

    2007-11-01

    The aim of the present study was to propose a strategy for the implementation of a Process Analytical Technology system in freeze-drying processes. Mannitol solutions, some of them supplied with NaCl, were used as models to freeze-dry. Noninvasive and in-line Raman measurements were continuously performed during lyophilization of the solutions to monitor real time the mannitol solid state, the end points of the different process steps (freezing, primary drying, secondary drying), and physical phenomena occurring during the process. At-line near-infrared (NIR) and X-ray powder diffractometry (XRPD) measurements were done to confirm the Raman conclusions and to find out additional information. The collected spectra during the processes were analyzed using principal component analysis and multivariate curve resolution. A two-level full factorial design was used to study the significant influence of process (freezing rate) and formulation variables (concentration of mannitol, concentration of NaCl, volume of freeze-dried sample) upon freeze-drying. Raman spectroscopy was able to monitor (i) the mannitol solid state (amorphous, alpha, beta, delta, and hemihydrate), (ii) several process step end points (end of mannitol crystallization during freezing, primary drying), and (iii) physical phenomena occurring during freeze-drying (onset of ice nucleation, onset of mannitol crystallization during the freezing step, onset of ice sublimation). NIR proved to be a more sensitive tool to monitor sublimation than Raman spectroscopy, while XRPD helped to unravel the mannitol hemihydrate in the samples. The experimental design results showed that several process and formulation variables significantly influence different aspects of lyophilization and that both are interrelated. Raman spectroscopy (in-line) and NIR spectroscopy and XRPD (at-line) not only allowed the real-time monitoring of mannitol freeze-drying processes but also helped (in combination with experimental design) us

  6. Effect of mixing time, freeze-drying and baking on phenolics, anthocyanins and antioxidant capacity of raspberry juice during processing of muffins.

    PubMed

    Rosales-Soto, Maria U; Powers, Joseph R; Alldredge, J Richard

    2012-05-01

    Consumption of baked products constitutes an important part of a daily breakfast considering that people are continually grabbing meals on the go. Among baked products, muffins rank third in breakfast products and attract a broad range of consumers. Incorporation of red raspberry juice into muffins can add value to the product while preserving health benefits to the consumer. The purpose of this study was to evaluate the effect of mixing time, freeze-drying and baking on the phenolic and anthocyanin contents and antioxidant capacity of raspberry juice during the preparation of muffins. Freeze-drying of raspberry batters reduced their phenolic content and antioxidant capacity regardless of mixing time. Non-freeze-dried raspberry batter mixed for 5 min had the highest phenolic content (0.88 mg gallic acid equivalent g(-1) dry matter (DM)). Non-freeze-dried raspberry muffins had the highest antioxidant capacity (0.041 µmol Trolox equivalent g(-1) DM). Freeze-dried raspberry batters mixed for 5 and 10 min had the highest anthocyanin content (0.065 mg cyanidin-3-glucoside g(-1) DM). Baking reduced the anthocyanin content of both non-freeze-dried and freeze-dried raspberry muffins. Despite the reduction in valuable compounds, muffin is a vehicle for the delivery of these compounds. Copyright © 2012 Society of Chemical Industry.

  7. Robust Vacuum-/Air-Dried Graphene Aerogels and Fast Recoverable Shape-Memory Hybrid Foams.

    PubMed

    Li, Chenwei; Qiu, Ling; Zhang, Baoqing; Li, Dan; Liu, Chen-Yang

    2016-02-17

    New graphene aerogels can be fabricated by vacuum/air drying, and because of the mechanical robustness of the graphene aerogels, shape-memory polymer/graphene hybrid foams can be fabricated by a simple infiltration-air-drying-crosslinking method. Due to the superelasticity, high strength, and good electrical conductivity of the as-prepared graphene aerogels, the shape-memory hybrid foams exhibit excellent thermotropical and electrical shape-memory properties, outperforming previously reported shape-memory polymer foams. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Cold Vacuum Drying facility civil structural system design description (SYS 06)

    SciT

    PITKOFF, C.C.

    This document describes the Cold Vacuum Drying (CVD) Facility civil - structural system. This system consists of the facility structure, including the administrative and process areas. The system's primary purpose is to provide for a facility to house the CVD process and personnel and to provide a tertiary level of containment. The document provides a description of the facility and demonstrates how the design meets the various requirements imposed by the safety analysis report and the design requirements document.

  9. New model for colour kinetics of plum under infrared vacuum condition and microwave drying.

    PubMed

    Chayjan, Reza Amiri; Alaei, Behnam

    2016-01-01

    Quality of dried foods is affected by the drying method and physiochemical changes in tissue. The drying method affects properties such as colour. The colour of processed food is one of the most important quality indices and plays a determinant role in consumer acceptability of food materials and the processing method. The colour of food materials can be used as an indirect factor to determine changes in quality, since it is simpler and faster than chemical methods. The study focused on the kinetics of colour changes of plum slices, under infrared vacuum and microwave conditions. Drying the samples was implemented at the absolute pressures of 20 and 60 kPa, drying temperatures of 50 and 60°C and microwave power of 90, 270, 450 and 630 W. Colour changes were quantified by the tri-stimulus L* (whiteness/darkness), a* (redness/greenness) and b* (yellowness/blueness) model, which is an international standard for color measurement developed by the Commission Internationale d'Eclairage (CIE). These values were also used to calculate total colour change (∆E), chroma, hue angle, and browning index (BI). A new model was used for mathematical modelling of colour change kinetics. The drying process changed the colour parameters of L*, a*, and b*, causing a colour shift toward the darker region. The values of L* and hue angle decreased, whereas the values of a*, b*, ∆E, chroma and browning index increased during exposure to infrared vacuum conditions and microwave drying. Comparing the results obtained using the new model with two conventional models of zero-order and first-order kinetics indicated that the new model presented more compatibility with the data of colour kinetics for all colour parameters and drying conditions. All kinetic changes in colour parameters can be explained by the new model presented in this study. The hybrid drying system included infrared vacuum conditions and microwave power for initial slow drying of plum slices and provided the desired

  10. Improvement of a dry formulation of Pseudomonas fluorescens EPS62e for fire blight disease biocontrol by combination of culture osmoadaptation with a freeze-drying lyoprotectant.

    PubMed

    Cabrefiga, J; Francés, J; Montesinos, E; Bonaterra, A

    2014-10-01

    To study the effect of lyoprotectants and osmoadaptation on viability of Pseudomonas fluorescens EPS62e during freeze-drying and storage and to evaluate the formulation in terms of efficacy in biocontrol and fitness on pear flowers. A wettable powder formulation of a biocontrol agent of fire blight was optimized by means of lyoprotectants and culture osmoadaptation. Freeze-drying was used to obtain dehydrated cells, and the best viability (70% of survival) was obtained using lactose as lyoprotectant. Survival during lyophilization was additionally improved using physiological adaptation of cells during cultivation under salt-amended medium (osmoadaptation). The procedure increased the survival of cells after freeze-drying attaining viability values close to a 100% in the lactose-formulated product (3 × 10(11) CFU g(-1) ), and through the storage period of 1 year at 4°C. The dry formulation showed also an improved biocontrol efficacy and survival of EPS62e on pear flowers under low relative humidity conditions. Cell viability after freeze-drying was improved using lactose as lyoprotectant combined with a procedure of osmoadaptation during cultivation. The powder-formulated product remained active for 12 months and retained biocontrol levels similar to that of fresh cells. The formulation showed an improved survival of EPS62e on flowers and an increase of the efficacy of biocontrol of fire blight at low relative humidity. The results have a potential value for commercial application in biocontrol agents not only of fire blight but also of other plant diseases. © 2014 The Society for Applied Microbiology.

  11. Effect of sugar additives on stability of human serum albumin during vacuum foam drying and storage.

    PubMed

    Hajare, A A; More, H N; Pisal, S S

    2011-11-01

    No literature on the protein stabilization of human serum albumin (HSA) by vacuum foam drying (VFD) has been reported. The purpose of this study was to investigate the effect of sugar-additive systems on the stability of HSA by VFD. For the assessment, HSA was formulated with sucrose and mannitol, respectively, alone or in combination with stabilizers, which were vacuum foam dried and stored at 25C. Protein content of the resulting dried formulations was analyzed by Lowry method. Fourier-transform infrared spectroscopy (FT-IR) analysis of the HSA secondary structure showed apparent protein structure-stabilizing effects of the amorphous sugar and phosphate combination during the VFD. In particular, sucrose-sodium phosphate monobasic mixture provide an interesting alternative to pure saccharide formulations due to their high glass transition temperatures and their increased ability to maintain a low melting transition temperature in the presence of small amounts of water. Inhibition of the sucrose crystallization in solutions under vacuum resulted in highly amorphous sucrose. Changes in the endothermic melting transition suggested reduced sucrose molecular mobility with increase in the sodium phosphate ratio. The addition of phosphate salts to sugar systems has several interesting features that merit its consideration in formulations to protect dehydrated labile biomaterials. In conclusion, our data suggest that sucrose and phosphate as additives seem to protect HSA during VFD better than lyophilized products and also maintain its stability in the VFD state during storage.

  12. Freeze-dried plasma at the point of injury: from concept to doctrine.

    PubMed

    Glassberg, Elon; Nadler, Roy; Gendler, Sami; Abramovich, Amir; Spinella, Philip C; Gerhardt, Robert T; Holcomb, John B; Kreiss, Yitshak

    2013-12-01

    While early plasma transfusion for the treatment of patients with ongoing major hemorrhage is widely accepted as part of the standard of care in the hospital setting, logistic constraints have limited its use in the out-of-hospital setting. Freeze-dried plasma (FDP), which can be stored at ambient temperatures, enables early treatment in the out-of-hospital setting. Point-of-injury plasma transfusion entails several significant advantages over currently used resuscitation fluids, including the avoidance of dilutional coagulopathy, by minimizing the need for crystalloid infusion, beneficial effects on endothelial function, physiological pH level, and better maintenance of intravascular volume compared with crystalloid-based solutions. The Israel Defense Forces Medical Corps policy is that plasma is the resuscitation fluid of choice for selected, severely wounded patients and has thus included FDP as part of its armamentarium for use at the point of injury by advanced life savers, across the entire military. We describe the clinical rationale behind the use of FDP at the point-of-injury, the drafting of the administration protocol now being used by Israel Defense Forces advanced life support providers, the process of procurement and distribution, and preliminary data describing the first casualties treated with FDP at the point of injury. It is our hope that others will be able to learn from our experience, thus improving trauma casualty care around the world.

  13. The stabilisation of purified, reconstituted P-glycoprotein by freeze drying with disaccharides.

    PubMed

    Heikal, Adam; Box, Karl; Rothnie, Alice; Storm, Janet; Callaghan, Richard; Allen, Marcus

    2009-02-01

    The drug efflux pump P-glycoprotein (P-gp) (ABCB1) confers multidrug resistance, a major cause of failure in the chemotherapy of tumours, exacerbated by a shortage of potent and selective inhibitors. A high throughput assay using purified P-gp to screen and characterise potential inhibitors would greatly accelerate their development. However, long-term stability of purified reconstituted ABCB1 can only be reliably achieved with storage at -80 degrees C. For example, at 20 degrees C, the activity of ABCB1 was abrogated with a half-life of <1 day. The aim of this investigation was to stabilise purified, reconstituted ABCB1 to enable storage at higher temperatures and thereby enable design of a high throughput assay system. The ABCB1 purification procedure was optimised to allow successful freeze drying by substitution of glycerol with the disaccharides trehalose or maltose. Addition of disaccharides resulted in ATPase activity being retained immediately following lyophilisation with no significant difference between the two disaccharides. However, during storage trehalose preserved ATPase activity for several months regardless of the temperature (e.g. 60% retention at 150 days), whereas ATPase activity in maltose purified P-gp was affected by both storage time and temperature. The data provide an effective mechanism for the production of resilient purified, reconstituted ABCB1.

  14. Microencapsulation of ethanol extract propolis by maltodextrin and freeze-dried preparation

    NASA Astrophysics Data System (ADS)

    Mangiring, Getta Austin; Pratami, Diah Kartika; Hermansyah, Heri; Wijanarko, Anondho; Rohmatin, Etin; Sahlan, Muhamad

    2018-02-01

    Propolis has been known to have many benefits for human health, such as anti-cancer, anti-tumor, anti-oxidant, anti-bacterial, and anti-inflammatory. Currently in Indonesia there are quite a lot of propolis-based products, such as soap, toothpaste, skin cream, or health products in liquid form. However, there is still no propolis product in powder form. In this research, microencapsulation of propolis using maltodextrin coating with freeze drying method will be done. Propolis powder has been tested for polyphenols and it was found that crude propolis (175 ml : 75 gr) had the highest polyphenols content in powder form, 434,438 µg /mL. Soft propolis (125 ml : 125 gr) has 4.533% of moisture content, which was the lowest result in these study. And also, the soft propolis (125 ml : 125 gr) has the highest solubility in water with 69% as the result. Propolis powder that has the highest solubility can be seen morphology using Scanning Electron Mocroscope (SEM). The result of the SEM test showed that the propolised powder form did not alter the morphology of maltodextrin. This indicates the success of microencapsulation, because the form of the coating agent maltodextrin was also not uniform.

  15. Toxic effect of ethylene-oxide-sterilized freeze-dried bone allograft on human gingival fibroblasts.

    PubMed

    Kudryk, V L; Scheidt, M J; McQuade, M J; Sutherland, D E; VanDyke, T E; Hollinger, J O

    1992-11-01

    Freeze-dried bone allograft (FDBA) which either had or had not been sterilized by exposure to ethylene oxide (EtO) prior to lyophilization was obtained from two commercial sources. EtO-sterilized FDBA was reexposed to EtO as a positive control. Gas chromatograph assays revealed that three out of four commercially obtained EtO sterilized FDBA had no detectable EtO, with one sample having 0.21 parts per million (PPM). Surprisingly, 0.24 PPM was detected in one sample which had not been sterilized with EtO gas. This was presumed due to contamination from a gas-sterilized rubber stopper. In the cell toxicity study, FDBA and human gingival fibroblasts (HGF) were added simultaneously, incubated for 72 h, and fixed and stained. Samples of FDBA sterilized with EtO which were free of EtO did not alter HGF growth. However, the positive control FDBA which contained 0.72 PPM EtO had a deleterious effect on HGF. FDBA with EtO residuals caused morphologic change in HGF.

  16. Dietary feeding of freeze-dried whole cranberry inhibits intestinal tumor development in Apcmin/+ mice

    PubMed Central

    Dong, Wenxiao; Zhang, Yujie; Wang, Sinan; Xie, Runxiang; Wang, Bangmao; Cao, Hailong

    2017-01-01

    It is increasingly perceived that dietary components have been linked with the prevention of intestinal cancer. Cranberry is a rich source of phenolic constituents and non-digestible fermentable dietary fiber, which shows anti-proliferation effect in colorectal cancer cells. Herein, we investigated the efficacy of long-term cranberry diet on intestinal adenoma formation in Apcmin/+ mice. Apcmin/+ mice were fed a basal diet or a diet containing 20% (w/w) freeze-dried whole cranberry powder for 12 weeks, and the number and size of tumors were recorded after sacrifice. Our results showed that cranberry strongly prevented the growth of intestinal tumors by 33.1%. Decreased cell proliferation and increased apoptosis were observed in tumors of cranberry-fed mice. Cranberry diet reduced the expression profile of colonic inflammatory cytokines (IFN-γ, IL-1β and TNF-α) accompanied with increased levels of anti-inflammatory cytokines (IL-4 and IL-10). Moreover, the number of colonic goblet cells and MUC2 production were increased, and the intestinal barrier function was also improved. In addition, cranberry diet increased caecal short chain fatty acids concentrations, and down-regulated epidermal growth factor receptor signaling pathway. These data firstly show the efficacy and associated mechanisms of cranberry diet on intestinal tumor growth in Apcmin/+ mice, suggesting its chemopreventive potential against intestinal cancer. PMID:29228651

  17. Impacts of compression on crystallization behavior of freeze-dried amorphous sucrose.

    PubMed

    Imamura, Koreyoshi; Nomura, Mayo; Tanaka, Kazuhiro; Kataoka, Nobuhide; Oshitani, Jun; Imanaka, Hiroyuki; Nakanishi, Kazuhiro

    2010-03-01

    An amorphous matrix comprised of sugar molecules is used as excipient and stabilizing agent for labile ingredients in the pharmaceutical industry. The amorphous sugar matrix is often compressed into a tablet form to reduce the volume and improve handling. Herein, the effect of compression on the crystallization behavior of an amorphous sucrose matrix was investigated. Amorphous sucrose samples were prepared by freeze-drying and compressed under different conditions, followed by analyses by differential scanning calorimetry, isothermal crystallization tests, X-ray powder diffractometry, Fourier transform infrared spectroscopy (FTIR), and gas pycnometry. The compressed sample had a lower crystallization temperature and a shorter induction period for isothermal crystallization, indicating that compression facilitates the formation of the critical nucleus of a sucrose crystal. Based on FTIR and molecular dynamics simulation results, the conformational distortion of sucrose molecules due to the compression appears to contribute to the increase in the free energy of the system, which leads to the facilitation of critical nucleus formation. An isothermal crystallization test indicated an increase in the growth rate of sucrose crystals by the compression. This can be attributed to the transformation of the microstructure from porous to nonporous, as the result of compression. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  18. Model-Based PAT for Quality Management in Pharmaceuticals Freeze-Drying: State of the Art

    PubMed Central

    Fissore, Davide

    2017-01-01

    Model-based process analytical technologies can be used for the in-line control and optimization of a pharmaceuticals freeze-drying process, as well as for the off-line design of the process, i.e., the identification of the optimal operating conditions. This paper aims at presenting the state of the art in this field, focusing, particularly, on three groups of systems, namely, those based on the temperature measurement (i.e., the soft sensor), on the chamber pressure measurement (i.e., the systems based on the test of pressure rise and of pressure decrease), and on the sublimation flux estimate (i.e., the tunable diode laser absorption spectroscopy and the valveless monitoring system). The application of these systems for in-line process optimization (e.g., using a model predictive control algorithm) and to get a true quality by design (e.g., through the off-line calculation of the design space of the process) is presented and discussed. PMID:28224123

  19. Multi-scale mechanical response of freeze-dried collagen scaffolds for tissue engineering applications.

    PubMed

    Offeddu, Giovanni S; Ashworth, Jennifer C; Cameron, Ruth E; Oyen, Michelle L

    2015-02-01

    Tissue engineering has grown in the past two decades as a promising solution to unresolved clinical problems such as osteoarthritis. The mechanical response of tissue engineering scaffolds is one of the factors determining their use in applications such as cartilage and bone repair. The relationship between the structural and intrinsic mechanical properties of the scaffolds was the object of this study, with the ultimate aim of understanding the stiffness of the substrate that adhered cells experience, and its link to the bulk mechanical properties. Freeze-dried type I collagen porous scaffolds made with varying slurry concentrations and pore sizes were tested in a viscoelastic framework by macroindentation. Membranes made up of stacks of pore walls were indented using colloidal probe atomic force microscopy. It was found that the bulk scaffold mechanical response varied with collagen concentration in the slurry consistent with previous studies on these materials. Hydration of the scaffolds resulted in a more compliant response, yet lesser viscoelastic relaxation. Indentation of the membranes suggested that the material making up the pore walls remains unchanged between conditions, so that the stiffness of the scaffolds at the scale of seeded cells is unchanged; rather, it is suggested that thicker pore walls or more of these result in the increased moduli for the greater slurry concentration conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: part I, product temperature measurement.

    PubMed

    Tang, Xiaolin; Nail, Steven L; Pikal, Michael J

    2006-02-10

    This study examines the factors that may cause systematic errors in the manometric temperature measurement (MTM) procedure used to evaluate product temperature during primary drying. MTM was conducted during primary drying using different vial loads, and the MTM product temperatures were compared with temperatures directly measured by thermocouples. To clarify the impact of freeze-drying load on MTM product temperature, simulation of the MTM vapor pressure rise was performed, and the results were compared with the experimental results. The effect of product temperature heterogeneity in MTM product temperature determination was investigated by comparing the MTM product temperatures with directly measured thermocouple product temperatures in systems differing in temperature heterogeneity. Both the simulated and experimental results showed that at least 50 vials (5 mL) were needed to give sufficiently rapid pressure rise during the MTM data collection period (25 seconds) in the freeze dryer, to allow accurate determination of the product temperature. The product temperature is location dependent, with higher temperature for vials on the edge of the array and lower temperature for the vials in the center of the array. The product temperature heterogeneity is also dependent upon the freeze-drying conditions. In product temperature heterogeneous systems, MTM measures a temperature close to the coldest product temperature, even if only a small fraction of the samples have the coldest product temperature. The MTM method is valid even at very low product temperature (-45 degrees C).

  1. Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: Part I, product temperature measurement.

    PubMed

    Tang, Xiaolin; Nail, Steven L; Pikal, Michael J

    2006-03-01

    This study examines the factors that may cause systematic errors in the manometric temperature measurement (MTM) procedure used to evaluate product temperature during primary drying. MTM was conducted during primary drying using different vial loads, and the MTM product temperatures were compared with temperatures directly measured by thermocouples. To clarify the impact of freeze-drying load on MTM product temperatures, simulation of the MTM vapor pressure rise was performed, and the results were compared with the experimental results. The effect of product temperature heterogeneity in MTM product temperature determination was investigated by comparing the MTM product temperatures with directly measured thermocouple product temperatures in systems differing in temperature heterogeneity. Both the simulated and experimental results showed that at least 50 vials (5 mL) were needed to give sufficiently rapid pressure rise during the MTM data collection period (25 seconds) in the freeze dryer, to allow accurate determination of the product temperature. The product temperature is location dependent, with higher temperature for vials on the edge of the array and lower temperature for the vials in the center of the array. The product temperature heterogeneity is also dependent upon the freeze-drying conditions. In product temperature heterogeneous systems, MTM measures a temperature close to the coldest product temperature, even, if only a small fraction of the samples have the coldest product temperature. The MTM method is valid even at very low product temperature (-45°C).

  2. Quality properties and adsorption behavior of freeze-dried beef meat from the Biceps femoris and Semimembranosus muscles.

    PubMed

    Aykın, Elif; Erbaş, Mustafa

    2016-11-01

    The aim of this research was to determine the quality properties and adsorption behavior of freeze-dried beef meat from the Biceps femoris and Semimembranosus muscles. Most quality properties of both muscles were similar apart from total fat content. Freeze-dried meat pieces were kept in ten different equilibrium levels of relative humidity (2.0-97.3%) at 5, 15, 25 and 30°C. The experimental data were evaluated using BET (Brunauer-Emmett-Teller) and GAB (Guggenheim, Anderson and deBoer) models. The equilibrium moisture contents of freeze-dried Biceps femoris were lower than those of Semimembranosus at all water activities and temperature. The constants m0 and C of BET and GAB equations were determined to be between 6.27 and 8.07g/100g dry matter and 9.32-13.73, respectively. Constant k was about 0.90 at all temperatures, and the GAB equation exhibited a better fit to the experimental data of both muscles as a result of all %E values being approximately equal to 10%. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Apoptosis-like death was involved in freeze-drying-preserved fungus Mucor rouxii and can be inhibited by L-proline.

    PubMed

    Wang, Xiaoyun; Wang, Youzhi

    2016-02-01

    Freeze-drying is one of the most effective methods to preserve fungi for an extended period. However, it is associated with a loss of viability and shortened storage time in some fungi. This study evaluated the stresses that led to the death of freeze-dried Mucor rouxii by using cell apoptotic methods. The results showed there were apoptosis-inducing stresses, such as the generation of obvious intracellular reactive oxygen species (ROS) and metacaspase activation. Moreover, nuclear condensation and a delayed cell death peak were determined after rehydration and 24 h incubation in freeze-dried M. rouxii via a propidium iodide (PI) assay, which is similar to the phenomenon of cryopreservation-induced delayed-onset cell death (CIDOCD). Then, several protective agents were tested to decrease the apoptosis-inducing stresses and to improve the viability. Finally, it was found that 1.6 mM L-proline can effectively decrease the nuclear condensation rate and increase the survival rate in freeze-dried M. rouxii. (1) apoptosis-inducing factors occur in freeze-dried M. rouxii. (2) ROS and activated metacaspases lead to death in freeze-dried M. rouxii. (3)L-proline increases the survival rate of freeze-dried M. rouxii. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Applications of Headspace Moisture Analysis for Investigating the Water Dynamics within a Sealed Vial Containing Freeze-dried Material.

    PubMed

    Cook, Isobel Ann; Ward, Kevin Richard

    2011-01-01

    We compare frequency modulation spectroscopy (FMS) as a method of headspace water analysis with the method of Karl Fischer coulometric titration (KF), which is widely used in the analysis of residual water in a freeze-dried material. Parameters relating to the type of formulation (amorphous, crystalline) and the freeze-drying cycle (temperature, pressure, time) were investigated in relation to the resulting headspace moisture (HSM) and total water. We describe the effect of stopper treatment and storage conditions on the HSM levels observed using FMS as a non-destructive method, which also allowed individual vials to be reanalyzed at a series of time points as part of a long-term monitoring exercise. The results of this study enabled a better understanding of the effect of stopper type and pre-lyophilization treatment on the HSM levels both immediately after freeze-drying and upon subsequent storage of the sealed vials of lyophilized material at different temperatures. A clear, linear relationship was observed between HSM and KF values for vials containing freeze-dried sucrose, implying a relatively straightforward interaction between water and the lyophilized cake for this material. Moisture mapping of all vials on one shelf of the freeze-dryer enabled further information to be obtained on the relationship of the formulation, vial, process conditions, equipment geometry, and performance on the intra-batch variability in HSM level and dynamics. It is believed that this could therefore represent a potentially useful technique for quality assurance and in the validation of lyophilization cycles, equipment, and scale-up. Lyophilization, also known as "freeze-drying," is a relatively old technique that has been used in its most basic form for thousands of years (e.g., preservation of fish and meat products). In its more advanced form it is used to preserve many medical products, for example, many vaccines are not stable in solution and therefore need to be dried to

  5. Effect of freeze-drying on viability and in vitro probiotic properties of a mixture of lactic acid bacteria and yeasts isolated from kefir.

    PubMed

    Bolla, Patricia A; Serradell, María de los Angeles; de Urraza, Patricio J; De Antoni, Graciela L

    2011-02-01

    The effect of freeze-drying on viability and probiotic properties of a microbial mixture containing selected bacterial and yeast strains isolated from kefir grains (Lactobacillus kefir, Lactobacillus plantarum, Lactococcus lactis, Saccharomyces cerevisiae and Kluyveromyces marxianus) was studied. The microorganisms were selected according to their potentially probiotic properties in vitro already reported. Two types of formulations were performed, a microbial mixture (MM) suspended in milk and a milk product fermented with MM (FMM). To test the effect of storage on viability of microorganisms, MM and FMM were freeze-dried and maintained at 4°C for six months. After 180 days of storage at 4°C, freeze-dried MM showed better survival rates for each strain than freeze-dried FMM. The addition of sugars (trehalose or sucrose) did not improve the survival rates of any of the microorganisms after freeze-drying. Freeze-drying did not affect the capacity of MM to inhibit growth of Shigella sonnei in vitro, since the co-incubation of this pathogen with freeze-dried MM produced a decrease of 2 log in Shigella viability. The safety of freeze-dried MM was tested in mice and non-translocation of microorganisms to liver or spleen was observed in BALB/c mice feed ad libitum during 7 or 20 days. To our knowledge, this is the first report about the effect of freeze-drying on viability, in vitro probiotic properties and microbial translocation of a mixture containing different strains of both bacteria and yeasts isolated from kefir.

  6. Evaluation of tunable diode laser absorption spectroscopy for in-process water vapor mass flux measurements during freeze drying.

    PubMed

    Gieseler, Henning; Kessler, William J; Finson, Michael; Davis, Steven J; Mulhall, Phillip A; Bons, Vincent; Debo, David J; Pikal, Michael J

    2007-07-01

    The goal of this work was to demonstrate the use of Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure the water vapor concentration and the vapor flow velocity in the spool connecting a freeze-dryer chamber and condenser. The instantaneous measurements were used to determine the water vapor mass flow rate (g/s). The mass flow determinations provided a continuous measurement of the total amount of water removed. Full load runs of pure water at different pressure and shelf temperature settings and a 5% (w/w) mannitol product run were performed in both laboratory and pilot scale freeze dryers. The ratio of "gravimetric/TDLAS" measurements of water removed was 1.02 +/- 0.06. A theoretical heat transfer model was used to predict the mass flow rate and the model results were compared to both the gravimetric and TDLAS data. Good agreement was also observed in the "gravimetric/TDLAS" ratio for the 5% mannitol runs dried in both freeze dryers. The endpoints of primary and secondary drying for the product runs were clearly identified. Comparison of the velocity and mass flux profiles between the laboratory and pilot dryers indicated a higher restriction to mass flow for the lab scale freeze dryer. Copyright 2007 Wiley-Liss, Inc.

  7. Heat and mass transfer scale-up issues during freeze-drying, III: control and characterization of dryer differences via operational qualification tests.

    PubMed

    Rambhatla, S; Tchessalov, S; Pikal, Michael J

    2006-04-21

    The objective of this research was to estimate differences in heat and mass transfer between freeze dryers due to inherent design characteristics using data obtained from sublimation tests. This study also aimed to provide guidelines for convenient scale-up of the freeze-drying process. Data obtained from sublimation tests performed on laboratory-scale, pilot, and production freeze dryers were used to evaluate various heat and mass transfer parameters: nonuniformity in shelf surface temperatures, resistance of pipe, refrigeration system, and condenser. Emissivity measurements of relevant surfaces such as the chamber wall and the freeze dryer door were taken to evaluate the impact of atypical radiation heat transfer during scale-up. "Hot" and "cold" spots were identified on the shelf surface of different freeze dryers, and the impact of variation in shelf surface temperatures on the primary drying time and the product temperature during primary drying was studied. Calculations performed using emissivity measurements on different freeze dryers suggest that a front vial in the laboratory lyophilizer received 1.8 times more heat than a front vial in a manufacturing freeze dryer operating at a shelf temperature of -25 degrees C and a chamber pressure of 150 mTorr during primary drying. Therefore, front vials in the laboratory are much more atypical than front vials in manufacturing. Steady-state heat and mass transfer equations were used to study a combination of different scale-up issues pertinent during lyophilization cycles commonly used for the freeze-drying of pharmaceuticals.

  8. Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: part II measurement of dry-layer resistance.

    PubMed

    Tang, Xiaolin Charlie; Nail, Steven L; Pikal, Michael J

    2006-01-01

    The purpose of this work was to study the factors that may cause systematic errors in the manometric temperature measurement (MTM) procedure used to determine product dry-layer resistance to vapor flow. Product temperature and dry-layer resistance were obtained using MTM software installed on a laboratory freeze-dryer. The MTM resistance values were compared with the resistance values obtained using the "vial method." The product dry-layer resistances obtained by MTM, assuming fixed temperature difference (DeltaT; 2 degrees C), were lower than the actual values, especially when the product temperatures and sublimation rates were low, but with DeltaT determined from the pressure rise data, more accurate results were obtained. MTM resistance values were generally lower than the values obtained with the vial method, particularly whenever freeze-drying was conducted under conditions that produced large variations in product temperature (ie, low shelf temperature, low chamber pressure, and without thermal shields). In an experiment designed to magnify temperature heterogeneity, MTM resistance values were much lower than the simple average of the product resistances. However, in experiments where product temperatures were homogenous, good agreement between MTM and "vial-method" resistances was obtained. The reason for the low MTM resistance problem is the fast vapor pressure rise from a few "warm" edge vials or vials with low resistance. With proper use of thermal shields, and the evaluation of DeltaT from the data, MTM resistance data are accurate. Thus, the MTM method for determining dry-layer resistance is a useful tool for freeze-drying process analytical technology.

  9. Optimization of the freeze-drying cycle: adaptation of the pressure rise analysis model to non-instantaneous isolation valves.

    PubMed

    Chouvenc, P; Vessot, S; Andrieu, J; Vacus, P

    2005-01-01

    The principal aim of this study is to extend to a pilot freeze-dryer equipped with a non-instantaneous isolation valve the previously presented pressure rise analysis (PRA) model for monitoring the product temperature and the resistance to mass transfer of the dried layer during primary drying. This method, derived from the original MTM method previously published, consists of interrupting rapidly (a few seconds) the water vapour flow from the sublimation chamber to the condenser and analysing the resulting dynamics of the total chamber pressure increase. The valve effect on the pressure rise profile observed during the isolation valve closing period was corrected by introducing in the initial PRA model a valve characteristic function factor which turned out to be independent of the operating conditions. This new extended PRA model was validated by implementing successively the two types of valves and by analysing the pressure rise kinetics data with the corresponding PRA models in the same operating conditions. The coherence and consistency shown on the identified parameter values (sublimation front temperature, dried layer mass transfer resistance) allowed validation of this extended PRA model with a non-instantaneous isolation valve. These results confirm that the PRA method, with or without an instantaneous isolation valve, is appropriate for on-line monitoring of product characteristics during freeze-drying. The advantages of PRA are that the method is rapid, non-invasive, and global. Consequently, PRA might become a powerful and promising tool not only for the control of pilot freeze-dryers but also for industrial freeze-dryers equipped with external condensers.

  10. Role of precursors on greening in crushed garlic (Allium sativum) bulbs, and its control with freeze-dried onion powder.

    PubMed

    Cho, Jungeun; Lee, Eun Jin; Yoo, Kil Sun; Lee, Seung Koo

    2012-01-30

    Lachrymatory factor (LF) synthase in onion bulbs reacts with S-1-propenyl-L-cysteine sulfoxide (1-PeCSO), a key compound in garlic greening. In this study, freeze-dried onion powder containing LF synthase was used in treatments to control garlic greening. Prior to the use of freeze-dried onion powder to treat greening garlic bulbs, model reactions were conducted to confirm the reactivity of 1-PeCSO in onion bulbs to garlic greening. While pink pigments were generated from 1-PeCSO, green pigments were produced from the combination of 1-PeCSO and S-2-propenyl-L-cysteine sulfoxide (2-PeCSO). However, pigments were formed in the systems containing 1-PeCSO, amino acid and alliinase. Even non-greening garlic bulbs stored at 20 °C turned green with the reaction of 200 g L(-1) 1-PeCSO; therefore 1-PeCSO isolated from onion bulbs had the same role as 1-PeCSO in garlic bulbs in terms of greening. Onion bulbs turned green after the addition of 600 g L(-1) 2-PeCSO. The addition of freeze-dried onion powder inhibited garlic greening, and treatment with 15 g kg(-1) onion powder gave the best storage stability of crushed garlic bulbs. The addition of freeze-dried onion powder inhibited the greening in crushed garlic bulbs, and treatment with 15 g kg(-1) onion powder gave the best storage stability of crushed garlic bulbs. Copyright © 2011 Society of Chemical Industry.

  11. A proposed rationale and test methodology for establishment of acceptance criteria for vacuum integrity testing of pharmaceutical freeze dryers.

    PubMed

    Hardwick, Lisa M; Nail, Steven L; Jarman, James; Hasler, Kai; Hense, Thomas

    2013-10-01

    A scientific rationale is proposed for the establishment of acceptance criteria for leak rates in pharmaceutical freeze dryers. A method was developed to determine the quantity of air that could leak into any lyophilizer from the outside while still maintaining Class 100/Grade A microbial conditions. A lyophilizing product is assumed most vulnerable to microbial contamination during secondary drying, when mass transfer of water vapor from product to condenser is minimal. Using the void volume of the dryer, calculated from change in internal pressure when a known volume of air is introduced, and the potential maximum bioburden of the leaked air (based on measured values), calculations can determine the allowable leaked volume of air, the flow rate required to admit that volume in a given time frame, and the pressure rise that would result from the leak over a given testing period. For the dryers in this study, using worst-case air quality conditions, it was determined that a leak resulting in a pressure rise of 0.027 mbar over a 30 min period would allow the dryers to remain in secondary drying conditions for 62 h before the established action level of one colony forming unit for each cubic meter of air space would be reached. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Effect of freezing, hot tumble drying and washing with eucalyptus oil on house dust mites in soft toys.

    PubMed

    Chang, Chin-Fu; Wu, Francis Fu-Sheng; Chen, Chi-Ying; Crane, Julian; Siebers, Rob

    2011-09-01

    Soft toys are a major source of house dust mites (HDM) and HDM allergens, and sleeping with soft toys is a significant risk factor for HDM sensitization. We studied three techniques to eliminate HDM from soft toys, namely freezing, hot tumble drying and washing with eucalyptus oil. Thirty-six toys (12 in each treatment group) were enumerated for live HDM by the heat escape method before and after freezing overnight, hot tumble drying for 1 h and washing in 0.2% to 0.4% eucalyptus oil. Freezing, hot tumble drying and washing with eucalyptus oil resulted in significant reductions in live HDM, an average reduction of 95.1%, 89.1% and 95.1%, respectively. Additionally, washing with eucalyptus oil resulted in a significant reduction in HDM allergens as well from a geometric mean of 9.12 μg/g to 0.37 μg/g (p = 0.033). These three HDM elimination techniques give parents of infants effective and acceptable methods of limiting HDM exposure. © 2011 John Wiley & Sons A/S.

  13. Impact behaviour of freeze-dried and fresh pomelo (Citrus maxima) peel: influence of the hydration state

    PubMed Central

    Thielen, Marc; Speck, Thomas; Seidel, Robin

    2015-01-01

    Pomelos (Citrus maxima) are known for their thick peel which—inter alia—serves as energy dissipator when fruits impact on the ground after being shed. It protects the fruit from splitting open and thus enables the contained seeds to stay germinable and to potentially be dispersed by animal vectors. The main part of the peel consists of a parenchymatous tissue that can be interpreted from a materials point of view as open pored foam whose struts are pressurized and filled with liquid. In order to investigate the influence of the water content on the energy dissipation capacity, drop weight tests were conducted with fresh and with freeze-dried peel samples. Based on the coefficient of restitution it was found that freeze-drying markedly reduces the relative energy dissipation capacity of the peel. Measuring the transmitted force during impact furthermore indicated a transition from a uniform collapse of the foam-like tissue to a progressive collapse due to water extraction. Representing the peel by a Maxwell model illustrates that freeze-drying not only drastically reduces the damping function of the dashpots but also stiffens the springs of the model. PMID:26543566

  14. THE INTRARENAL DISTRIBUTION OF TRITIATED PARA-AMINOHIPPURIC ACID DETERMINED BY A MODIFIED TECHNIQUE OF SECTION FREEZE-DRY RADIOAUTOGRAPHY

    PubMed Central

    Bordier, Betrand; Ornstein, Leonard; Wedeen, Richard P.

    1970-01-01

    Section freeze-dry radioautography has been used to examine the intrarenal distribution of a water-soluble organic acid (para-aminohippuric acid (PAH-3H)) under constant-infusion, steady-state conditions in mouse and rat kidney in vivo. The technique described here has the following advantages: (a) Sectioning and freeze-drying are accomplished in a closed cryostat at temperatures below -40°C; (b) Handling of the section is facilitated by mounting of the section-to-be on adhesive-coated Saran Wrap prior to cutting; (c) Unembedded freeze-dried sections are attached to photographic film at ambient temperature in the dark room; (d) Fixation follows completion of radioautographic exposure and precedes photographic development; (e) Permanent close contact is maintained between tissue and film. Morphologic preservation compared favorably with that obtained by optimal fixation techniques, which, however, permit diffusion. Cellular accumulation of PAH-3H during secretion was demonstrated in the proximal tubule under steady-state conditions in vivo. The cellular concentration of PAH-3H was uniform throughout the length of the proximal tubule in mouse and rat kidney. PMID:4349130

  15. PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.

    PubMed

    Ahmed, Iman S; El-Hosary, Rania; Shalaby, Samia; Abd-Rabo, Marwa M; Elkhateeb, Dalia G; Nour, Samia

    2016-05-17

    In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized. The pharmacodynamics (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs formulations showing acceptable long-term stability were determined and compared to a marketed AC immediate release tablet (Lipitor(®)) in albino rats. PD results revealed that the two tested formulations were equally effective in reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given in reduced doses compared to Lipitor(®) and showed no adverse effects. PK results, on the other hand, revealed that the two freeze-dried AC-NPs formulations were of significantly lower bioavailability compared to Lipitor(®). Taken together the PD and PK results demonstrate that the improved efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to increased concentration of AC in the liver rather than in the plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Solidification of liposomes by freeze-drying: the importance of incorporating gelatin as interior support on enhanced physical stability.

    PubMed

    Guan, Peipei; Lu, Yi; Qi, Jianping; Niu, Mengmeng; Lian, Ruyue; Wu, Wei

    2015-01-30

    The main purpose of this study was to investigate the effect of gelatin as interior support on the physical stability of freeze-dried liposomes. Anticancer agent paclitaxel (PTX) was selected as a model drug. Freeze-dried liposomes containing interior gelatin support (GLs) were prepared by thin-film dispersion/freeze-drying method. Several properties of the GLs, including entrapment efficiency, particle size and gelation temperature, were extensively characterized. Encapsulation efficiency of conventional liposomes (CLs) and liposomes containing lyoprotectants as interior support dropped to lower than 20% after reconstitution, while GLs still maintained an entrapment efficiency of over 84%. Scanning electron microscopy revealed well preserved liposomal structure of GLs after reconstitution. Meanwhile, the particle size and entrapment efficiency of GLs were also well preserved after reconstitution. In contrary, deformation of CLs and recrystallization of PTX were observed, as well as significant changes in particle size and entrapment efficiency. Taken together, interior gelatin support obviously enhanced the physical stability of liposomes against the lyophilization stress. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Spray-Freeze Drying: a Suitable Method for Aerosol Delivery of Antibodies in the Presence of Trehalose and Cyclodextrins.

    PubMed

    Pouya, Maryam Amini; Daneshmand, Behnaz; Aghababaie, Shabnam; Faghihi, Homa; Vatanara, Alireza

    2018-05-08

    We aimed to prepare spray-freeze-dried powder of IgG considering physicochemical stability and aerodynamic aspects. Spray-freeze drying (SFD) exposes proteins to various stresses which should be compensated by suitable stabilizers. The competence of cyclodextrins (CDs), namely beta-cyclodextrin (βCD) and hydroxypropyl βCD (HPβCD), at very low concentrations, was investigated in the presence of separate mannitol- and trehalose-based formulations. Spray-freeze-dried preparations were quantified in terms of monomer recovery and conformation by size exclusion chromatography (SEC-HPLC) and Fourier transform infrared (FTIR) spectroscopy, respectively. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) were employed to identify the thermal characteristics of powders. Particle morphology was visualized by scanning electron microscopy (SEM). Aerodynamic behavior of powders was checked through an Anderson cascade impactor (ACI). Although all formulations protected antibody from aggregation during the SFD process (aggregation < 1%), mannitol-containing ones failed upon the storage (19.54% in the worst case). Trehalose-HPβCD incomparably preserved the formulation with fine particle fraction (FPF) of 51.29%. Crystallization of mannitol resulted in IgG destabilization upon storage. Although employed concentration of CDs is too low (less than 50:1 molar ratio to protein), they successfully served as stabilizing agents in SFD with perfect improvement in aerosol functionality. Graphical Abstract ᅟ.

  18. Critically safe volume vacuum pickup for use in wet or dry cleanup of radioactive enclosures

    DOEpatents

    Zeren, Joseph D.

    1993-12-28

    A physical compact vacuum pickup device of critically safe volume and geometric shape is provided for use in radioactive enclosures, such as a small glove box, to facilitate manual cleanup of either wet or dry radioactive material. The device is constructed and arranged so as to remain safe when filled to capacity with plutonium-239 oxide. Two fine mesh filter bags are supported on the exterior of a rigid fine mesh stainless steel cup. This assembly is sealed within, and spaced from, the interior walls of a stainless steel canister. An air inlet communicates with the interior of the canister. A modified conventional vacuum head is physically connected to, and associated with, the interior of the mesh cup. The volume of the canister, as defined by the space between the mesh cup and the interior walls of the canister, forms a critically safe volume and geometric shape for dry radioactive particles that are gathered within the canister. A critically safe liquid volume is maintained by operation of a suction terminating float valve, and/or by operation of redundant vacuum check/liquid drain valves and placement of the air inlet.

  19. Critically safe volume vacuum pickup for use in wet or dry cleanup of radioactive enclosures

    DOEpatents

    Zeren, J.D.

    1993-12-28

    A physical compact vacuum pickup device of critically safe volume and geometric shape is provided for use in radioactive enclosures, such as a small glove box, to facilitate manual cleanup of either wet or dry radioactive material. The device is constructed and arranged so as to remain safe when filled to capacity with plutonium-239 oxide. Two fine mesh filter bags are supported on the exterior of a rigid fine mesh stainless steel cup. This assembly is sealed within, and spaced from, the interior walls of a stainless steel canister. An air inlet communicates with the interior of the canister. A modified conventional vacuum head is physically connected to, and associated with, the interior of the mesh cup. The volume of the canister, as defined by the space between the mesh cup and the interior walls of the canister, forms a critically safe volume and geometric shape for dry radioactive particles that are gathered within the canister. A critically safe liquid volume is maintained by operation of a suction terminating float valve, and/or by operation of redundant vacuum check/liquid drain valves and placement of the air inlet. 5 figures.

  20. Evaluation of freeze-dried kefir coculture as starter in feta-type cheese production.

    PubMed

    Kourkoutas, Y; Kandylis, P; Panas, P; Dooley, J S G; Nigam, P; Koutinas, A A

    2006-09-01

    The use of freeze-dried kefir coculture as a starter in the production of feta-type cheese was investigated. Maturation of the produced cheese at 4 degrees C was monitored for up to 70 days, and the effects of the starter culture, the salting method, and the ripening process on quality characteristics were studied. The use of kefir coculture as a starter led to increased lactic acid concentrations and decreased pH values in the final product associated with significantly higher conversion rates compared to salted rennet cheese. Determination of bacterial diversity at the end of the ripening process in salted kefir and rennet cheeses by denaturing gradient gel electrophoresis technology, based on both DNA and RNA analyses, suggested a potential species-specific inhibition of members of the genera Staphylococcus and Psychrobacter by kefir coculture. The main active microbial associations in salted kefir cheese appeared to be members of the genera Pseudomonas and Lactococcus, while in salted rennet cheese, Oxalobacteraceae, Janthinobacterium, Psychrobacter, and Pseudomonas species were noted. The effect of the starter culture on the production of aroma-related compounds responsible for cheese flavor was also studied by the solid-phase microextraction-gas chromatography-mass spectrometry technique. Kefir coculture also appeared to extend the shelf life of unsalted cheese. Spoilage of kefir cheese was observed on the 9th and 20th days of preservation at 10 and 5 degrees C, respectively, while spoilage in the corresponding rennet cheese was detected on the 7th and 16th days. Microbial counts during preservation of both types of unsalted cheese increased steadily and reached similar levels, with the exception of staphylococci, which were significantly lower in unsalted kefir cheese. All types of cheese produced with kefir as a starter were approved and accepted by the panel during the preliminary sensory evaluation compared to commercial feta-type cheese.

  1. Use of freeze-dried plasma in French intensive care unit in Afghanistan.

    PubMed

    Martinaud, Christophe; Ausset, Sylvain; Deshayes, Anne Virginie; Cauet, Amandine; Demazeau, Nicolas; Sailliol, Anne

    2011-12-01

    Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.

  2. Trace elements in a commercial freeze-dried human urine reference material.

    PubMed

    Veillon, C; Patterson, K Y

    1996-07-01

    A large batch of freeze-dried human urine reference material, Seronorm Trace Elements Urine, Lot 101021, was prepared commercially (Nycomed Pharma AS, Oslo, Norway) for quality control purposes in trace element analysis. Analytes are being determined by a voluntary, international co-operative effort so that the material will be available to the scientific community at modest cost. The material is in stoppered glass vials and is to be reconstituted with 5.00 ml of water prior to use. We have evaluated the trace element content for several elements, including chromium and zinc, elements for which we have two independent methods available for the determinations, namely isotope dilution mass spectrometry (IDMS) and atomic absorption spectrometry (AAS). We also report on other trace elements measured by IDMS alone, such as Se, for which we have enriched stable isotopes available. Results for chromium indicate a mean +/- standard deviation (n = 10) of 1.2 +/- 0.3 (by IDMS) and 1.4 +/- 0.3 (by AAS) ng Cr per ml of reconstituted urine, indicating possible inhomogeneity and/or contamination (21-25% relative standard deviation, RSD). Approximately half of the observed chromium originates from the sample container. The values observed for zinc were 590 +/- 90 ng ml-1 (15% RSD) for freshly reconstituted material, 760 +/- 60 ng ml-1 (8% RSD) for material reconstituted 4 d earlier, and 940 +/- 60 ng ml-1 (6% RSD) 2 months after reconstitution. Selenium values by IDMS were very reproducible, with a mean concentration of 16 +/- 0.15 ng g-1 (0.9% RSD), suggesting little or no contamination and a high degree of sample homogeneity for this element. The source of potential contaminants has been evaluated by multielement determinations of leachates of the vials and stoppers. Elements noted in significant amounts include B, Ba, Sr, Mo, Cu and Zn, with most of the zinc coming from the rubber stopper.

  3. In vitro evaluation of demineralized freeze-dried bone allograft in combination with enamel matrix derivative.

    PubMed

    Miron, Richard J; Bosshardt, Dieter D; Laugisch, Oliver; Dard, Michel; Gemperli, Anja C; Buser, Daniel; Gruber, Reinhard; Sculean, Anton

    2013-11-01

    Preclinical and clinical studies suggest that a combination of enamel matrix derivative (EMD) with demineralized freeze-dried bone allograft (DFDBA) may improve periodontal wound healing and regeneration. To date, no single study has characterized the effects of this combination on in vitro cell behavior. The aim of this study is to test the ability of EMD to adsorb to the surface of DFDBA particles and determine the effect of EMD coating on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. DFDBA particles were precoated with EMD or human blood and analyzed for protein adsorption patterns via scanning electron microscopy. Cell attachment and proliferation were quantified using a commercial assay. Cell differentiation was analyzed using real-time polymerase chain reaction for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen 1α1, and mineralization was assessed using alizarinred staining. Analysis of cell attachment revealed no significant differences among control, blood-coated, and EMD-coated DFDBA particles. EMD significantly increased cell proliferation at 3 and 5 days after seeding for both osteoblasts and PDL cells compared to control and blood-coated samples. Moreover, there were significantly higher messenger ribonucleic acid levels of osteogenic differentiation markers, including collagen 1α1, alkaline phosphatase, and osteocalcin, in osteoblasts and PDL cells cultured on EMD-coated DFDBA particles at 3, 7, and 14 days. The results suggest that the addition of EMD to DFDBA particles may influence periodontal regeneration by stimulating PDL cell and osteoblast proliferation and differentiation.

  4. Prediction of glass transition temperature of freeze-dried formulations by molecular dynamics simulation.

    PubMed

    Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

    2003-06-01

    To examine whether the glass transition temperature (Tg) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of dextran, and alpha-glucose, the repeated unit of dextran. in the presence or absence of water molecules. Estimated values of Tg were compared with experimental values obtained by differential scanning calorimetry (DSC). Isothermal-isobaric molecular dynamics simulations (NPTMD) and isothermal molecular dynamics simulations at a constant volume (NVTMD) were carried out using the software package DISCOVER (Material Studio) with the Polymer Consortium Force Field. Mean-squared displacement and radial distribution function were calculated. NVTMD using the values of density obtained by NPTMD provided the diffusivity of glucose-ring oxygen and water oxygen in amorphous alpha-glucose and isomaltodecaose, which exhibited a discontinuity in temperature dependence due to glass transition. Tg was estimated to be approximately 400K and 500K for pure amorphous a-glucose and isomaltodecaose, respectively, and in the presence of one water molecule per glucose unit, Tg was 340K and 360K, respectively. Estimated Tg values were higher than experimentally determined values because of the very fast cooling rates in the simulations. However, decreases in Tg on hydration and increases in Tg associated with larger fragment size could be demonstrated. The results indicate that molecular dynamics simulation is a useful method for investigating the effects of hydration and molecular weight on the Tg of lyophilized formulations containing polymer excipients. although the relationship between cooling rates and Tg must first be elucidated to predict Tg vales observed by DSC measurement. January 16.

  5. [Optimization of trehalose loading in red blood cells before freeze-drying].

    PubMed

    Zhuang, Yuan; Liu, Jing-Han; Ouyang, Xi-Lin; Chen, Lin-Feng; Che, Ji

    2007-04-01

    The key points for better protection of trehalose in freeze-drying red blood cells (RBCs) are to resolve non-osmosis of trehalose to red blood cells and to make cytoplasmic trehalose to reach effective concentration. This study was aimed to investigate the regularity of loading RBCs with trehalose, screen out optimal loading condition and evaluate the effect of trehalose on physico-chemical parameters of RBCs during the period of loading. The cytoplasmic trehalose concentration in red blood cells, free hemoglobin and ATP level were determined at different incubation temperatures (4, 22 and 37 degrees C), different trehaolse concentrations (0, 200, 400, 600, 800 and 1000 mmol/L) and different incubation times (2, 4, 6, 8 and 10 hours), the cytoplasmic trehalose, free hemoglobin (FHb), hemoglobin (Hb) and mean corpuscular volume (MCV) in fresh RBCs and RBCs stored for 72 hours at 4 degrees C were compared, when loading condition was ensured. The results showed that with increase of incubation temperature, time and extracellular trehalose concentration, the loading of trehalose in RBCs also increased. Under the optimal loading condition, cytoplasmic trehalose concentration and free hemoglobin level of fresh RBCs and RBCs stored for 72 hours at 4 degrees C were 65.505 +/- 6.314 mmol/L, 66.2 +/- 5.002 mmol/L and 6.567 +/- 2.568 g/L, 16.168 +/- 3.922 g/L respectively. It is concluded that the most optimal condition of loading trehalose is that fresh RBCs incubate in 800 mmol/L trehalose solution for 8 hours at 37 degrees C. This condition can result in a efficient cytoplasmic trehalose concentration. The study provides an important basis for long-term preservation of RBCs.

  6. The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model.

    PubMed

    Xie, Ling; Zhong, Xiaohong; Liu, Dongbo; Liu, Lin; Xia, Zhilan

    2017-12-01

    Conventional scientific studies had supported the use of polysaccharides and β-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-β1 (TGF-β1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4 + CD25 + Foxp3 + (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P < 0.01). The application of middle- and high-dose FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid-related orphan receptor gamma t(RORγt) mRNA. High-dose FDPGLM possibly plays a role in ROU by promoting CD4 + CD25 + Foxp3 + Treg and inhibiting T helper cell 17 differentiation. This study also shows that FDPGLM may be potentially used as a complementary and alternative medicine treatment scheme for ROU.

  7. Freeze-drying of tert-butyl alcohol/water cosolvent systems: effects of formulation and process variables on residual solvents.

    PubMed

    Wittaya-Areekul, S; Nail, S L

    1998-04-01

    The objective of this study was to identify significant formulation and processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems. The variables examined were the physical state of the solute (crystalline vs amorphous), initial TBA concentration, freezing rate, cake thickness, and the temperature and duration of secondary drying. Sucrose and glycine were used as models for noncrystallizing and crystallizing solutes, respectively. The TBA concentration above which eutectic crystallization takes place was determined by differential scanning calorimetry. Model formulations were subjected to extremes of freezing rate by either dipping in liquid nitrogen or by slowly freezing on the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was determined by withdrawing samples as a function of time at different shelf temperatures using a thief system. On the basis of these studies, the most important determinant of residual TBA level is the physical state of the solute. Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%) regardless of freezing rate or initial TBA concentration. For freeze-dried sucrose, residual TBA levels were approximately 2 orders of magnitude higher and were significantly affected by initial TBA concentration and freezing rate. For the sucrose/TBA/water system, relatively low residual TBA levels were obtained when the initial TBA level was above the threshold concentration for eutectic crystallization of TBA, whereas samples freeze-dried from solutions containing TBA concentrations below this threshold contained significantly higher levels of TBA. Residual IPA levels increased continuously with initial concentration of TBA in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were frozen rapidly contained residual TBA levels which were approximately twice those measured in the same

  8. Headspace Moisture Mapping and the Information That Can Be Gained about Freeze-Dried Materials and Processes.

    PubMed

    Cook, Isobel A; Ward, Kevin R

    2011-01-01

    Regulatory authorities require proof that lyophilization (freeze drying) cycles have been developed logically and demonstrate uniformity. One measure of uniformity can be consistency of residual water content throughout a batch. In primary drying, heat transfer is effected by gaseous convection and conduction as well as the degree of shelf contact and evenness of heat applied; therefore residual water can be affected by container location, degree of container/tray/shelf contact, radiative heating, packing density, product formulation, and the cycle conditions themselves. In this study we have used frequency modulation spectroscopy (FMS) to create a map of headspace moisture (HSM) for 100% of vials within a number of freeze-dried batches. Karl Fischer (KF)/HSM correlations were investigated in parallel with the moisture mapping studies. A clear, linear relationship was observed between HSM and KF values for vials containing freeze-dried sucrose, implying a relatively straightforward interaction between water and the lyophilized cake for this material. Mannitol demonstrated a more complex correlation, with the interaction of different crystalline forms giving important information on the uniformity of the material produced. It was observed that annealing had a significant impact on the importance of heat transfer by conduction for vials in direct and non-direct contact with the shelf. Moisture mapping of all vials within the freeze dryer enabled further information to be obtained on the relationship of the formulation, process conditions, and equipment geometry on the intra-batch variability in HSM level. The ability of FMS to allow 100% inspection could mean that this method could play an important part in process validation and quality assurance. Lyophilization, also known as freeze drying, is a relatively old technique that has been used in its most basic form for thousands of years (e.g., preservation of fish and meat products). In its more advanced form it is

  9. Process Analytical Technology in Freeze-Drying: Detection of the Secondary Solute + Water Crystallization with Heat Flux Sensors.

    PubMed

    Wang, Qiming; Shalaev, Evgenyi

    2018-04-01

    In situ and non-invasive detection of solute crystallization during freeze-drying would facilitate cycle optimization and scale-up from the laboratory to commercial manufacturing scale. The objective of the study is to evaluate heat flux sensor (HFS) as a tool for monitoring solute crystallization and other first-order phase transitions (e.g., onset of freezing). HFS is a thin-film differential thermopile, which acts as a transducer to generate an electrical signal proportional to the total heat applied to its surface. In this study, HFS is used to detect both primary (ice formation) and secondary (also known as eutectic) solute + water crystallization during cooling and heating of solutions in a freeze-dryer. Binary water-solute mixtures with typical excipients concentrations (e.g., 0.9% of NaCl and 5% mannitol) and fill volumes (1 to 3 ml/vial) are studied. Secondary crystallization is detected by the HFS during cooling in all experiments with NaCl solutions, whereas timing of mannitol crystallization depends on the cooling conditions. In particular, mannitol crystallization takes place during cooling, if the cooling rate is lower than the critical value. On the other hand, if the cooling rate exceeds the critical cooling rate, mannitol crystallization during cooling is prevented, and crystallization occurs during subsequent warming or annealing. It is also observed that, while controlled ice nucleation allows initiation of the primary freezing event in different vials simultaneously, there is a noticeable vial-to-vial difference in the timing of secondary crystallization. The HFS could be a valuable process monitoring tool for non-invasive detection of various crystallization events during freeze-drying manufacturing.

  10. Relevance of nanocomposite packaging on the stability of vacuum-packed dry cured ham.

    PubMed

    Lloret, Elsa; Fernandez, Avelina; Trbojevich, Raul; Arnau, Jacint; Picouet, Pierre A

    2016-08-01

    In this study effects of a novel high barrier multilayer polyamide film containing dispersed nanoclays (PAN) on the stability of vacuum packed dry-cured ham were investigated during 90days refrigerated storage in comparison with non-modified multilayer polyamide (PA) and a commercial high barrier film. Characteristic bands of the mineral in FT-IR spectra confirmed the presence of nanoclays in PAN, enhancing oxygen transmission barrier properties and UV protection. Packaging in PAN films did not originate significant changes on colour or lipid oxidation during prolonged storage of vacuum-packed dry-cured ham. Larger oxygen transmission rates in PA films caused changes in CIE b* during refrigerated storage. Ham quality was not affected by light exposition during 90days and only curing had a significant benefit on colour and TBARS, being cured samples more stable during storage in all the packages used. Packaging of dry-cured ham in PAN was equivalent to commercial high barrier films. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Vacuum Drying for Extending Litchi Shelf-Life: Vitamin C, Total Phenolics, Texture and Shelf-Life Assessment.

    PubMed

    Richter Reis, Felipe; de Oliveira, Aline Caroline; Gadelha, Gabriella Giani Pieretti; de Abreu, Marcela Breves; Soares, Hillary Isabelle

    2017-06-01

    In an attempt to obtain shelf-stable litchi fruit with preserved nutritional quality and good sensory features, quarters of peeled and pitted fruits were vacuum dried at 50, 60 and 70 °C at a constant pressure of 8.0 kPa. The product was assessed for its vitamin C, total phenolics and texture (hardness). In addition, the product with the best texture was assessed for its shelf-life by means of accelerated testing. Results suggest that vacuum dried litchi retained almost 70% of the vitamin C and total phenolics when compared to frozen fruits (control). Vitamin C and phenolic compounds content significantly decreased with drying, while no difference was found between different drying temperatures. Hardness increased with drying temperature. The sample dried at 70 °C presented crispness, which is a desired quality feature in dried fruit products. This sample was subjected to shelf-life evaluation, whose result suggests a shelf-life of eight months at 23 °C. Total color change (CIE ΔE 00 ) was the expiry criterion. Vacuum drying was a suitable technique for producing shelf-stable litchi fruit with good texture while preserving its desirable original nutrients. Consumption of vacuum dried litchi may be beneficial to health due to its remarkable content of phenolic compounds and vitamin C.

  12. Raman microscopy of freeze-dried mouse eyeball-slice in conjunction with the "in vivo cryotechnique".

    PubMed

    Terada, Nobuo; Ohno, Nobuhiko; Saitoh, Sei; Fujii, Yasuhisa; Ohguro, Hiroshi; Ohno, Shinichi

    2007-07-01

    The wavelength of Raman-scattered light depends on the molecular composition of the substance. This is the first attempt to acquire Raman spectra of a mouse eyeball removed from a living mouse, in which the eyeball was preserved using the "in vivo cryotechnique" followed by freeze-drying. Eyeballs were cryofixed using a rapid freezing cryotechnique, and then sliced in the cryostat machine. The slices were sandwiched between glass slides, freeze-dried, and analyzed with confocal Raman microscopy. Important areas including various eyeball tissue layers were selected using bright-field microscopy, and then the Raman spectra were obtained at 240 locations. Four typical patterns of Raman spectra were electronically mapped on the specimen images obtained by the bright-field microscopy. Tissue organization was confirmed by embedding the same eyeball slice used for Raman spectra into epoxy resin and the thick sections were prepared with the inverted capsule method. Each Raman spectral pattern represents a different histological layer in the eyeball which was mapped by comparing the images of toluidine blue staining and Raman mapping with different colors. In the choroid and pigment cell layer, the Raman spectrum had two peaks, corresponding to melanin. Some of the peaks of the Raman spectra obtained from the blood vessels in sclera and the photoreceptor layer were similar to those obtained from the purified hemoglobin and rhodopsin proteins, respectively. Our experimental protocol can distinguish different tissue components with Raman microscopy; therefore, this method can be very useful for examining the distribution of a biological structures and/or chemical components in rapidly frozen freeze-dried tissue.

  13. Synthesis of high-performance Li2FeSiO4/C composite powder by spray-freezing/freeze-drying a solution with two carbon sources

    NASA Astrophysics Data System (ADS)

    Fujita, Yukiko; Iwase, Hiroaki; Shida, Kenji; Liao, Jinsun; Fukui, Takehisa; Matsuda, Motohide

    2017-09-01

    Li2FeSiO4 is a promising cathode active material for lithium-ion batteries due to its high theoretical capacity. Spray-freezing/freeze-drying, a practical process reported for the synthesis of various ceramic powders, is applied to the synthesis of Li2FeSiO4/C composite powders and high-performance Li2FeSiO4/C composite powders are successfully synthesized by using starting solutions containing both Indian ink and glucose as carbon sources followed by heating. The synthesized composite powders have a unique structure, composed of Li2FeSiO4 nanoparticles coated with a thin carbon layer formed by the carbonization of glucose and carbon nanoparticles from Indian ink. The carbon layer enhances the electrochemical reactivity of the Li2FeSiO4, and the carbon nanoparticles play a role in the formation of electron-conducting paths in the cathode. The composite powders deliver an initial discharge capacity of 195 and 137 mAh g-1 at 0.1 C and 1 C, respectively, without further addition of conductive additive. The discharge capacity at 1 C is 72 mAh g-1 after the 100th cycle, corresponding to approximately 75% of the capacity at the 2nd cycle.

  14. Influence of Freeze-Drying and Oven-Drying Post Blanching on the Nutrient Composition of the Edible Insect Ruspolia differens

    PubMed Central

    Fombong, Forkwa Tengweh; Van Der Borght, Mik; Vanden Broeck, Jozef

    2017-01-01

    The longhorn grasshopper, Ruspolia differens (Serville), plays an important role as a food source across Sub-Saharan Africa, where it is consumed as a delicacy in both rural and urban areas. The effect of two drying methods (freeze-drying and oven-drying), employed after blanching, on the proximate, fatty acid and mineral composition of the two most common morphs was determined. Ruspolia differens grasshoppers were harvested in Uganda and Kenya from wild swarms during the rainy periods of November–December 2016. Based on cuticular coloration, we identified three morphs, green, brown and purple, which occurred at a ratio of 65:33:2, respectively. Results indicated that these insects have a high lipid content of 36%, as well as significant protein levels ranging between 33% and 46% dry matter. Oleic acid (44%) and palmitic acid (28%) were the two most abundant fatty acids; while the presence of arachidonic acid (0.6%) and docosahexaenoic acid (0.21%) suggests that Ruspolia differens is also a source of polyunsaturated fatty acids. The observed amino acid profile showed similar trends in all morphs, and all essential amino acids were present. Calcium (896–1035 mg/100 g), potassium (779–816 mg/100 g) and phosphorus (652–685 mg/100 g) were quite high among the minerals. The presence of the trace elements iron (217–220 mg/100 g), zinc (14.2–14.6 mg/100 g), manganese (7.4–8.3 mg/100 g) and copper (1.66 mg/100 g) suggests that inclusion of these grasshoppers in human diets may aid in combatting micronutrient deficiencies. Oven-drying Ruspolia differens delivered the same nutritional quality as freeze-drying. Hence, both drying approaches can be adequately used to formulate insect-based food products without noticeable nutritional changes. PMID:28926949

  15. Influence of Freeze-Drying and Oven-Drying Post Blanching on the Nutrient Composition of the Edible Insect Ruspolia differens.

    PubMed

    Fombong, Forkwa Tengweh; Van Der Borght, Mik; Vanden Broeck, Jozef

    2017-09-16

    The longhorn grasshopper, Ruspolia differens (Serville), plays an important role as a food source across Sub-Saharan Africa, where it is consumed as a delicacy in both rural and urban areas. The effect of two drying methods (freeze-drying and oven-drying), employed after blanching, on the proximate, fatty acid and mineral composition of the two most common morphs was determined. Ruspolia differens grasshoppers were harvested in Uganda and Kenya from wild swarms during the rainy periods of November-December 2016. Based on cuticular coloration, we identified three morphs, green, brown and purple, which occurred at a ratio of 65:33:2, respectively. Results indicated that these insects have a high lipid content of 36%, as well as significant protein levels ranging between 33% and 46% dry matter. Oleic acid (44%) and palmitic acid (28%) were the two most abundant fatty acids; while the presence of arachidonic acid (0.6%) and docosahexaenoic acid (0.21%) suggests that Ruspolia differens is also a source of polyunsaturated fatty acids. The observed amino acid profile showed similar trends in all morphs, and all essential amino acids were present. Calcium (896-1035 mg/100 g), potassium (779-816 mg/100 g) and phosphorus (652-685 mg/100 g) were quite high among the minerals. The presence of the trace elements iron (217-220 mg/100 g), zinc (14.2-14.6 mg/100 g), manganese (7.4-8.3 mg/100 g) and copper (1.66 mg/100 g) suggests that inclusion of these grasshoppers in human diets may aid in combatting micronutrient deficiencies. Oven-drying Ruspolia differens delivered the same nutritional quality as freeze-drying. Hence, both drying approaches can be adequately used to formulate insect-based food products without noticeable nutritional changes.

  16. The impact of freeze-drying infant fecal samples on measures of their bacterial community profiles and milk-derived oligosaccharide content.

    PubMed

    Lewis, Zachery T; Davis, Jasmine C C; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B; Mills, David A

    2016-01-01

    Infant fecal samples are commonly studied to investigate the impacts of breastfeeding on the development of the microbiota and subsequent health effects. Comparisons of infants living in different geographic regions and environmental contexts are needed to aid our understanding of evolutionarily-selected milk adaptations. However, the preservation of fecal samples from individuals in remote locales until they can be processed can be a challenge. Freeze-drying (lyophilization) offers a cost-effective way to preserve some biological samples for transport and analysis at a later date. Currently, it is unknown what, if any, biases are introduced into various analyses by the freeze-drying process. Here, we investigated how freeze-drying affected analysis of two relevant and intertwined aspects of infant fecal samples, marker gene amplicon sequencing of the bacterial community and the fecal oligosaccharide profile (undigested human milk oligosaccharides). No differences were discovered between the fecal oligosaccharide profiles of wet and freeze-dried samples. The marker gene sequencing data showed an increase in proportional representation of Bacteriodes and a decrease in detection of bifidobacteria and members of class Bacilli after freeze-drying. This sample treatment bias may possibly be related to the cell morphology of these different taxa (Gram status). However, these effects did not overwhelm the natural variation among individuals, as the community data still strongly grouped by subject and not by freeze-drying status. We also found that compensating for sample concentration during freeze-drying, while not necessary, was also not detrimental. Freeze-drying may therefore be an acceptable method of sample preservation and mass reduction for some studies of microbial ecology and milk glycan analysis.

  17. Fast freeze-drying cycle design and optimization using a PAT based on the measurement of product temperature.

    PubMed

    Bosca, Serena; Barresi, Antonello A; Fissore, Davide

    2013-10-01

    This paper is focused on the use of an innovative Process Analytical Technology for the fast design and optimization of freeze-drying cycles for pharmaceuticals. The tool is based on a soft-sensor, a device that uses the experimental measure of product temperature during freeze-drying, a mathematical model of the process, and the Extended Kalman Filter algorithm to estimate the sublimation flux, the residual amount of ice in the vial, and some model parameters (heat and mass transfer coefficients). The accuracy of the estimations provided by the soft-sensor has been shown using as test case aqueous solutions containing different excipients (sucrose, polyvinylpyrrolidone), processed at various operating conditions, pointing out that the soft-sensor allows a fast estimation of model parameters and product dynamics without involving expensive hardware or time consuming analysis. The possibility of using the soft-sensor to calculate in-line (or off-line) the design space of the primary drying phase is here presented and discussed. Results evidences that by this way, it is possible to identify the values of the heating fluid temperature that maintain product temperature below the limit value, as well as the operating conditions that maximize the sublimation flux. Various experiments have been carried out to test the effectiveness of the proposed approach for a fast design of the cycle, evidencing that drying time can be significantly reduced, without impairing product quality. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Effect of amino acids on the stability of spray freeze-dried immunoglobulin G in sugar-based matrices.

    PubMed

    Emami, Fakhrossadat; Vatanara, Alireza; Najafabadi, Abdolhosein Rouholamini; Kim, Yejin; Park, Eun Ji; Sardari, Soroush; Na, Dong Hee

    2018-07-01

    The purpose of this study was to prepare spray freeze-dried particles of immunoglobulin G (IgG) using various combinations of trehalose and different amino acids (leucine, phenylalanine, arginine, cysteine, and glycine), and investigate the effect of the amino acids on the stability of IgG during the spray freeze-drying (SFD) process and storage. The morphology and structural integrity of the processed particles were evaluated by physical and spectroscopic techniques. SFD-processed IgG without any excipient resulted in the formation of aggregates corresponding to approximately 14% of IgG. In contrast, IgG formulations stabilized using an optimal level of leucine, phenylalanine, or glycine in the presence of trehalose displayed aggregates <2.2%. In particular, phenylalanine combined with trehalose was most effective in stabilizing IgG against shear, freezing, and dehydration stresses during SFD. Arginine and cysteine were destabilizers displaying aggregation and fragmentation of IgG, respectively. Aggregation and fragmentation were evaluated by dynamic light scattering, ultraviolet spectrophotometry, size-exclusion chromatography, and microchip capillary gel electrophoresis. The IgG formulations prepared with leucine, phenylalanine, or glycine in the presence of trehalose showed good stability after storage at 40 °C and 75% relative humidity for 2 months. Thus, a combination of the excipients trehalose and uncharged, nonpolar amino acids appears effective for production of stable SFD IgG formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Uptake of erythromycin by first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), fed live or freeze-dried enriched adult Artemia or medicated pellets.

    PubMed

    Cook, M A; Rust, M B; Massee, K; Majack, T; Peterson, M E

    2003-05-01

    The potential to use adult Artemia to deliver erythromycin to first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), was investigated in three trials. In the first trial, first-feeding sockeye were fed live erythromycin enriched adult Artemia or pellets containing equal amounts of erythromycin for 35 days. At the end of the trial, tissue erythromycin concentration of the fish fed the live Artemia was significantly greater (P < 0.05, 25.52 +/- 1.29 microg mL(-1); mean +/- SEM), than the tissue concentration of the fish fed the pellets (0.72 +/- 0.01 microg mL(-1)). In the second trial, first-feeding sockeye were fed either live or freeze-dried bioencapsulated erythromycin (adult Artemia) or pellets containing erythromycin daily for 21 days. Mean daily erythromycin concentration in fish fed the freeze-dried Artemia, live Artemia, or pellets did not differ significantly. In the third trial, apparent erythromycin digestibility was determined. Significantly more (P < 0.05) erythromycin was retained by juvenile sockeye fed freeze-dried bioencapsulated erythromycin (98.3 +/- 1.0%) compared with medicated pellets (89.2 +/- 1.7%). Uptake of bioencapsulated erythromycin from adult Artemia (live or freeze-dried) appears to be greater than uptake from pellets. Freeze-dried and live Artemia were equally effective at delivery suggesting enriched freeze-dried adult Artemia could be produced into a highly palatable, consistent, off-the-shelf product.

  20. Dry powder inhalers: physicochemical and aerosolization properties of several size-fractions of a promising alterative carrier, freeze-dried mannitol.

    PubMed

    Kaialy, Waseem; Nokhodchi, Ali

    2015-02-20

    The purpose of this work was to evaluate the physicochemical and inhalation characteristics of different size fractions of a promising carrier, i.e., freeze-dried mannitol (FDM). FDM was prepared and sieved into four size fractions. FDMs were then characterized in terms of micromeritic, solid-state and bulk properties. Dry powder inhaler (DPI) formulations were prepared using salbutamol sulphate (SS) and then evaluated in terms of drug content homogeneity and in vitro aerosolization performance. The results showed that the crystalline state of mannitol was maintained following freeze-drying for all size fractions of FDM. All FDM particles showed elongated morphology and contained mixtures of α-, β- and δ-mannitol. In comparison to small FDM particles, FDMs with larger particle sizes demonstrated narrower size distributions, higher bulk and tap densities, lower porosities and better flowability. Regardless of particle size, all FDMs generated a significantly higher (2.2-2.9-fold increase) fine particle fraction (FPF, 37.5 ± 0.9%-48.6 ± 2.8%) of SS in comparison to commercial mannitol. The FPFs of SS were related to the shape descriptors of FDM particles; however, FPFs did not prove quantitative apparent relationships with either particle size or powder bulk descriptors. Large FDM particles were more favourable than smaller particles because they produced DPI formulations with better flowability, better drug content homogeneity, lower amounts of the drug depositing on the throat and contained lower fine-particle-mannitol. Optimized stable DPI formulations with superior physicochemical and pharmaceutical properties can be achieved using larger particles of freeze-dried mannitol (FDM). Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Lipid and protein oxidation and sensory properties of vacuum-packaged dry-cured ham subjected to high hydrostatic pressure.

    PubMed

    Fuentes, Verónica; Ventanas, Jesús; Morcuende, David; Estévez, Mario; Ventanas, Sonia

    2010-07-01

    The effect of HHP treatment (600 MPa) on the oxidative stability of lipids and proteins of vacuum-packaged Iberian dry-cured ham and the impact on the sensory characteristics of the product was investigated. In order to assess how different commercial presentations are affected by HHP treatment, three different presentations of vacuum-packaged Iberian dry-cured ham were considered, namely, (i) intact format (IF) corresponding to non-sliced vacuum-packaged dry-cured ham, (ii) conventional-sliced format (CSF) corresponding to dry-cured ham slices placed stretched out in the package and (iii) alternative-sliced format (ASF) corresponding to dry-cured ham slices piled up horizontally. The oxidation of dry-cured ham lipids and proteins was enhanced by HHP-treatment with the presentation being highly influential on these oxidative reactions. Pre-slicing dry-cured ham results in a more susceptible product to oxidative reactions during pressurisation and subsequent refrigerated storage. Possible mechanisms, by which HHP-induced oxidative reactions would affect particular sensory traits in vacuum-packaged Iberian dry-cured ham such as colour, texture and flavour attributes, are discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Calculation of the process of vacuum drying of a metal-concrete container with spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Karyakin, Yu. E.; Lavrent'ev, S. A.; Pavlyukevich, N. V.; Pletnev, A. A.; Fedorovich, E. D.

    2012-01-01

    An algorithm and results of calculation of the process of vacuum drying of a metal-concrete container intended for long-term "dry" storage of spent nuclear fuel are presented. A calculated substantiation of the initial amount of moisture in the container is given.

  3. Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation.

    PubMed

    Schwartz, Z; Mellonig, J T; Carnes, D L; de la Fontaine, J; Cochran, D L; Dean, D D; Boyan, B D

    1996-09-01

    Demineralized freeze-dried bone allograft (DFDBA) has been used extensively in periodontal therapy. The rationale for use of DFDBA includes the fact that proteins capable of inducing new bone; i.e., bone morphogenetic proteins, can be isolated from bone grafts. Commercial bone banks have provided DFDBA to the dental practitioner for many years; however, these organizations have not verified the osteoinductive capacity of their DFDBA preparations. The aim of this study was to determine the ability of commercial DFDBA preparations to induce new bone formation. DFDBA with particle sizes ranging from 200 to 500 microns was received from six bone banks using various bone production methods. Different lots of DFDBA from the same tissue bank were sometimes available. A total of 14 lots were examined. The surface area of bone particles in each sample was measured morphometrically and the pH of a solution containing the particles after suspension in distilled water determined. Samples from each DFDBA lot were implanted intramuscularly (10 mg) or subcutaneously (20 mg) into three different animals and tissue biopsies harvested after 4 weeks. One sample from each tissue bank was implanted and harvested after 8 weeks. At harvest, each area where DFDBA had been implanted was excised and examined by light microscopy. The ability of DFDBA to produce new bone was evaluated and the amount of residual bone particles measured. The results show that bone particles from all tissue banks had a variety of shapes and sizes, both before implantation and after 1 or 2 months of implantation. The pH of particle suspensions also varied between batches, as well as between tissue banks. None of the DFDBA induced new bone formation when implanted subcutaneously. Intramuscular implants from three banks induced new bone formation after 1 and 2 months. DFDBA from two banks caused new bone formation only after 2 months. However, DFDBA from one bank did not induce new bone at all. Particle size before

  4. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique.

    PubMed

    Gohel, Mukesh; Patel, Madhabhai; Amin, Avani; Agrawal, Ruchi; Dave, Rikita; Bariya, Nehal

    2004-04-26

    The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

  5. Consumer preference and effect of correct or misleading information after ageing beef longissimus muscle using vacuum, dry ageing, or a dry ageing bag.

    PubMed

    Stenström, Helena; Li, Xin; Hunt, Melvin C; Lundström, Kerstin

    2014-02-01

    The objective of this study was to determine which ageing treatment of beef was sensorially preferred by consumers and how their preference changed when given information about the ageing treatment used. Longissimus thoracis et lumborum from four young bulls were randomly assigned three ageing treatments: dry ageing, vacuum ageing and ageing in a highly moisture permeable bag (bag dry-ageing); each was aged at 1.6 °C for another 13 days. A preference test (171 consumers) with questions about overall liking, tenderness, and juiciness was performed. Thereafter, a deceptive test (61 consumers) was performed with two taste samples, the first taste sample with correct information about ageing treatment and the second with false information. In the preference test, consumers preferred dry ageing and bag dry-ageing to vacuum ageing. In the deceptive test, dry ageing was preferred, but the information given influenced preference. © 2013.

  6. Drying characteristics of whole Musa AA group ‘Kluai Leb Mu Nang’ using hot air and infrared vacuum

    NASA Astrophysics Data System (ADS)

    Kulketwong, C.; Thungsotanon, D.; Suwanpayak, N.

    2017-06-01

    Dried Musa AA group ‘Kluai Leb Mu Nang’ are the famous processing goods of Chumphon province, the south of Thailand. In this paper, we improved the qualities of whole Musa AA group ‘Kluai leb Mu Nang’ by using the hot air and infrared vacuum (HA and infrared vacuum) drying method which has two stages. The first stage of the method is the hot air (HA) and hot air-infrared (HAI) drying for rapidly reducing the moisture content and the drying times at atmospheric pressure, and the second stage, the moisture content, and color of the samples can be controlled by the HA and infrared vacuum drying. The experiment was evaluated by the terms of firmness, color change, moisture content, vacuum pressure and energy consumption at various temperatures. The results were found that the suitable temperature of the HAI and HA and infrared vacuum drying stages at 70°C and 55°C, respectively, while the suitable vacuum pressure in the second process was -0.4 bar. The samples were dried in a total of 28 hrs using 13.83 MJ/kg of specific energy consumption (stage 1 with 8.8 MJ/kg and stage 2 of 5.03 MJ/kg). The physical characteristics of the 21% (wb) of dried bananas can be measured the color change, L*=38.56, a*=16.47 and b*=16.3, was approximate the goods from the local market, whereas the firmness of them was more tender and shown a value of 849.56 kN/m3.

  7. SLUDGE TREATMENT PROJECT KOP DISPOSITION - THERMAL AND GAS ANALYSIS FOR THE COLD VACUUM DRYING FACILITY

    SciT

    SWENSON JA; CROWE RD; APTHORPE R

    2010-03-09

    The purpose of this document is to present conceptual design phase thermal process calculations that support the process design and process safety basis for the cold vacuum drying of K Basin KOP material. This document is intended to demonstrate that the conceptual approach: (1) Represents a workable process design that is suitable for development in preliminary design; and (2) Will support formal safety documentation to be prepared during the definitive design phase to establish an acceptable safety basis. The Sludge Treatment Project (STP) is responsible for the disposition of Knock Out Pot (KOP) sludge within the 105-K West (KW) Basin.more » KOP sludge consists of size segregated material (primarily canister particulate) from the fuel and scrap cleaning process used in the Spent Nuclear Fuel process at K Basin. The KOP sludge will be pre-treated to remove fines and some of the constituents containing chemically bound water, after which it is referred to as KOP material. The KOP material will then be loaded into a Multi-Canister Overpack (MCO), dried at the Cold Vacuum Drying Facility (CVDF) and stored in the Canister Storage Building (CSB). This process is patterned after the successful drying of 2100 metric tons of spent fuel, and uses the same facilities and much of the same equipment that was used for drying fuel and scrap. Table ES-l present similarities and differences between KOP material and fuel and between MCOs loaded with these materials. The potential content of bound water bearing constituents limits the mass ofKOP material in an MCO load to a fraction of that in an MCO containing fuel and scrap; however, the small particle size of the KOP material causes the surface area to be significantly higher. This relatively large reactive surface area represents an input to the KOP thermal calculations that is significantly different from the calculations for fuel MCOs. The conceptual design provides for a copper insert block that limits the volume

  8. The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process.

    PubMed

    Poursina, Narges; Vatanara, Alireza; Rouini, Mohammad Reza; Gilani, Kambiz; Najafabadi, Abdolhossein Rouholamini

    2016-06-01

    Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).

  9. Encapsulation of antioxidant phenolic compounds extracted from spent coffee grounds by freeze-drying and spray-drying using different coating materials.

    PubMed

    Ballesteros, Lina F; Ramirez, Monica J; Orrego, Carlos E; Teixeira, José A; Mussatto, Solange I

    2017-12-15

    Freeze-drying and spray-drying techniques were evaluated for encapsulation of phenolic compounds (PC) extracted from spent coffee grounds. Additionally, the use of maltodextrin, gum arabic and a mixture of these components (ratio 1:1) as wall material to retain the PC and preserve their antioxidant activity was also assessed. The contents of PC and flavonoids (FLA), as well as the antioxidant activity of the encapsulated samples were determined in order to verify the efficiency of each studied condition. Additional analyses for characterization of the samples were also performed. Both the technique and the coating material greatly influenced the encapsulation of antioxidant PC. The best results were achieved when PC were encapsulated by freeze-drying using maltodextrin as wall material. Under these conditions, the amount of PC and FLA retained in the encapsulated sample corresponded to 62% and 73%, respectively, and 73-86% of the antioxidant activity present in the original extract was preserved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor

    PubMed Central

    Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

    2014-01-01

    In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin. PMID:24729702

  11. Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor.

    PubMed

    Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

    2014-01-01

    In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin.

  12. Protein crowding in solution, frozen and freeze-dried states: small-angle neutron and X-ray scattering study of lysozyme/sorbitol/water systems

    NASA Astrophysics Data System (ADS)

    Krueger, Susan; Khodadadi, Sheila; Clark, Nicholas; McAuley, Arnold; Cristiglio, Viviana; Theyencheri, Narayanan; Curtis, Joseph; Shalaev, Evgenyi

    2015-03-01

    For effective preservation, proteins are often stored as frozen solutions or in glassy states using a freeze-drying process. However, aggregation is often observed after freeze-thaw or reconstitution of freeze-dried powder and the stability of the protein is no longer assured. In this study, small-angle neutron and X-ray scattering (SANS and SAXS) have been used to investigate changes in protein-protein interaction distances of a model protein/cryoprotectant system of lysozyme/sorbitol/water, under representative pharmaceutical processing conditions. The results demonstrate the utility of SAXS and SANS methods to monitor protein crowding at different stages of freezing and drying. The SANS measurements of solution samples showed at least one protein interaction peak corresponding to an interaction distance of ~ 90 Å. In the frozen state, two protein interaction peaks were observed by SANS with corresponding interaction distances at 40 Å as well as 90 Å. On the other hand, both SAXS and SANS data for freeze-dried samples showed three peaks, suggesting interaction distances ranging from ~ 15 Å to 170 Å. Possible interpretations of these interaction peaks will be discussed, as well as the role of sorbitol as a cryoprotectant during the freezing and drying process.

  13. In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complementary process analytical technology (PAT) tools.

    PubMed

    De Beer, T R M; Vercruysse, P; Burggraeve, A; Quinten, T; Ouyang, J; Zhang, X; Vervaet, C; Remon, J P; Baeyens, W R G

    2009-09-01

    The aim of the present study was to examine the complementary properties of Raman and near infrared (NIR) spectroscopy as PAT tools for the fast, noninvasive, nondestructive and in-line process monitoring of a freeze drying process. Therefore, Raman and NIR probes were built in the freeze dryer chamber, allowing simultaneous process monitoring. A 5% (w/v) mannitol solution was used as model for freeze drying. Raman and NIR spectra were continuously collected during freeze drying (one Raman and NIR spectrum/min) and the spectra were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR). Raman spectroscopy was able to supply information about (i) the mannitol solid state throughout the entire process, (ii) the endpoint of freezing (endpoint of mannitol crystallization), and (iii) several physical and chemical phenomena occurring during the process (onset of ice nucleation, onset of mannitol crystallization). NIR spectroscopy proved to be a more sensitive tool to monitor the critical aspects during drying: (i) endpoint of ice sublimation and (ii) monitoring the release of hydrate water during storage. Furthermore, via NIR spectroscopy some Raman observations were confirmed: start of ice nucleation, end of mannitol crystallization and solid state characteristics of the end product. When Raman and NIR monitoring were performed on the same vial, the Raman signal was saturated during the freezing step caused by reflected NIR light reaching the Raman detector. Therefore, NIR and Raman measurements were done on a different vial. Also the importance of the position of the probes (Raman probe above the vial and NIR probe at the bottom of the sidewall of the vial) in order to obtain all required critical information is outlined. Combining Raman and NIR spectroscopy for the simultaneous monitoring of freeze drying allows monitoring almost all critical freeze drying process aspects. Both techniques do not only complement each other, they also

  14. Comparative study of subtalar arthrodesis after calcaneal frature malunion with autologous bone graft or freeze-dried xenograft.

    PubMed

    Henning, Carlo; Poglia, Gabriel; Leie, Murilo Anderson; Galia, Carlos Roberto

    2015-12-01

    Calcaneal fracture malunion may evolve into arthrosis and severe foot deformities. The aim of this study was to identify differences in bony union following corrective subtalar arthrodesis with interposition of autologous tricortical bone graft or freeze-dried bovine xenograft. We prospectively evaluated 12 patients who underwent subtalar arthrodesis, six patients received autografts and 6 received freeze-dried bovine xenografts. After a mean followup of 58 weeks, the patients were clinical assessed using AOFAS scale and the visual analog scale (VAS) for pain and for final radiographic parameters measurement. Two blind raters evaluated the length of time required for solid union of the arthrodesis and graft integration by retrospective radiographic examination. In the autograft group, AOFAS score improved from a preoperative average of 37 to 64 points postoperatively (p = 0.02) and mean VAS score improved from 4.7 to 1.9 (p = 0.028). In the xenograft group, AOFAS score improved from 38 to 74 points (p = 0.02) and VAS from 5.5 to 2.7 (p = 0.046). Solid union was achieved in all cases in the autograft group at an average of 5.3 weeks and in five cases in the xenograft group at 8.8 weeks (p = 0.077). Graft integration occurred after an average of 10.7 weeks in the autograft group and 28.8 weeks in the xenograft group (p = 0.016). With the numbers available, no significant difference could be detected in the length of time required for solid union of subtalar arthrodesis between groups, although time to integration of freeze-dried bovine xenografts was statistically higher. Clinical and functional improvement was observed in both groups.

  15. Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

    PubMed

    Datta, N K; Das, K P; Alam, M S; Kaiser, M S

    2014-07-01

    Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is <0.001. Follow up period was 6 month to 11 years. From our study it was realized that freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow is useful graft material for healing of the lesional area as well as restoring structural integrity for the treatment of unicameral bone cyst.

  16. Effects of cryoprotectants on the viability and activity of freeze dried recombinant yeasts as novel oral drug delivery systems assessed by an artificial digestive system.

    PubMed

    Blanquet, Stéphanie; Garrait, Ghislain; Beyssac, Erick; Perrier, Céline; Denis, Sylvain; Hébrard, Géraldine; Alric, Monique

    2005-09-01

    The aim of this study was to investigate, in a gastric-small intestinal system TIM-1, the effect of cryoprotectants on the survival of freeze-dried Saccharomyces cerevisiae expressing the heterologous P450 73A1 and their ability to convert trans-cinnamic acid into p-coumaric acid. Yeasts were lyophilized in suspensions of trehalose, maltose, lactose, or a milk proteins/trehalose mix. Freeze-dried or native yeasts and trans-cinnamic acid were introduced simultaneously into TIM-1 at the beginning of digestion. Yeast survival rate was evaluated by cell counting in the ileal effluents. P450 73A1 activity was followed by HPLC assay of p-coumaric acid. Freeze-dried yeasts showed high tolerance to digestive conditions. Nevertheless, their survival rate was lower than that of non-dried cells (around 80% whatever the protective agent vs. 96%). The ability of recombinant freeze-dried S. cerevisiae to perform a bioconversion reaction in the digestive tract was shown with all the protectants. The highest trans-cinnamic acid conversion rate (24 vs. 41% for native yeasts) was obtained with the milk proteins/trehalose mix. These results show that freeze-drying might be considered for the pharmaceutical formulation of new drug delivery systems based on orally administered recombinant yeasts and that TIM-1 could be a helpful tool for the pre-screening of oral dosage forms.

  17. Dry matter partitioning and photosynthetic response to biennial bearing and freeze damage in 'Empire' apple

    Biennial cropping is typically characterized as having 'ON' and 'OFF' years in which the 'ON' year produces an excessive crop load and the 'OFF' year has a very small crop load. Frost damage during the bloom period or winter freeze damage are another means of reducing the crop load that can initiat...

  18. Meat quality, microbiological status and consumer preference of beef gluteus medius aged in a dry ageing bag or vacuum.

    PubMed

    Li, Xin; Babol, Jakub; Wallby, Anna; Lundström, Kerstin

    2013-10-01

    This study investigated meat quality and consumer preference after ageing beef gluteus medius in a water vapour-permeable dry-ageing bag or in vacuum for 14 days. Higher ageing and trim losses but lower thawing loss, cooking loss and water content were found in samples aged in dry ageing bags compared to those aged in vacuum. Samples aged in dry ageing bags had higher total bacteria and yeast counts but lower lactic acid bacteria counts than those aged in vacuum, both before and after trimming. Meat aged in dry ageing bag was more tender and juicier and overall preferred by consumers compared with samples aged in vacuum. Female participants outperformed the males in detecting differences in palatability. No differences were found in pH, smell, shear force, colour, Enterobacteriaceae, and mould counts. Thus, by using a dry ageing bag, it is possible to produce dry-aged meat in a more controlled condition without negative effects on sensory or other quality attributes. Copyright © 2013. Published by Elsevier Ltd.

  19. Global Sensitivity Analysis as Good Modelling Practices tool for the identification of the most influential process parameters of the primary drying step during freeze-drying.

    PubMed

    Van Bockstal, Pieter-Jan; Mortier, Séverine Thérèse F C; Corver, Jos; Nopens, Ingmar; Gernaey, Krist V; De Beer, Thomas

    2018-02-01

    Pharmaceutical batch freeze-drying is commonly used to improve the stability of biological therapeutics. The primary drying step is regulated by the dynamic settings of the adaptable process variables, shelf temperature T s and chamber pressure P c . Mechanistic modelling of the primary drying step leads to the optimal dynamic combination of these adaptable process variables in function of time. According to Good Modelling Practices, a Global Sensitivity Analysis (GSA) is essential for appropriate model building. In this study, both a regression-based and variance-based GSA were conducted on a validated mechanistic primary drying model to estimate the impact of several model input parameters on two output variables, the product temperature at the sublimation front T i and the sublimation rate ṁ sub . T s was identified as most influential parameter on both T i and ṁ sub , followed by P c and the dried product mass transfer resistance α Rp for T i and ṁ sub , respectively. The GSA findings were experimentally validated for ṁ sub via a Design of Experiments (DoE) approach. The results indicated that GSA is a very useful tool for the evaluation of the impact of different process variables on the model outcome, leading to essential process knowledge, without the need for time-consuming experiments (e.g., DoE). Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Reversed phase HPLC analysis of stability and microstructural effects on degradation kinetics of β-carotene encapsulated in freeze-dried maltodextrin-emulsion systems.

    PubMed

    Harnkarnsujarit, Nathdanai; Charoenrein, Sanguansri; Roos, Yrjö H

    2012-09-26

    Degradation of dispersed lipophilic compounds in hydrophilic solids depends upon matrix stability and lipid physicochemical properties. This study investigated effects of solid microstructure and size of lipid droplets on the stability of dispersed β-carotene in freeze-dried systems. Emulsions of β-carotene in sunflower oil were dispersed in maltodextrin systems (M040/DE6, M100/DE11, and M250/DE25.5) (8% w/w oil) and prefrozen at various freezing conditions prior to freeze-drying to control nucleation and subsequent pore size and structural collapse of freeze-dried solids. The particle size, physical state, and β-carotene contents of freeze-dried emulsions were measured during storage at various water activity (a(w)) using a laser particle size analyzer, differential scanning calorimeter, and high performance liquid chromatography (HPLC), respectively. The results showed that M040 stabilized emulsions in low temperature freezing exhibited lipid crystallization. Collapse of solids in storage at a(w) which plasticized systems to the rubbery state led to flow and increased the size of oil droplets. Degradation of β-carotene analyzed using a reversed-phase C(30) column followed first-order kinetics. Porosity of solids had a major effect on β-carotene stability; however, the highest stability was found in fully plasticized and collapsed solids.

  1. Freeze-drying simulation framework coupling product attributes and equipment capability: toward accelerating process by equipment modifications.

    PubMed

    Ganguly, Arnab; Alexeenko, Alina A; Schultz, Steven G; Kim, Sherry G

    2013-10-01

    A physics-based model for the sublimation-transport-condensation processes occurring in pharmaceutical freeze-drying by coupling product attributes and equipment capabilities into a unified simulation framework is presented. The system-level model is used to determine the effect of operating conditions such as shelf temperature, chamber pressure, and the load size on occurrence of choking for a production-scale dryer. Several data sets corresponding to production-scale runs with a load from 120 to 485 L have been compared with simulations. A subset of data is used for calibration, whereas another data set corresponding to a load of 150 L is used for model validation. The model predictions for both the onset and extent of choking as well as for the measured product temperature agree well with the production-scale measurements. Additionally, we study the effect of resistance to vapor transport presented by the duct with a valve and a baffle in the production-scale freeze-dryer. Computation Fluid Dynamics (CFD) techniques augmented with a system-level unsteady heat and mass transfer model allow to predict dynamic process conditions taking into consideration specific dryer design. CFD modeling of flow structure in the duct presented here for a production-scale freeze-dryer quantifies the benefit of reducing the obstruction to the flow through several design modifications. It is found that the use of a combined valve-baffle system can increase vapor flow rate by a factor of 2.2. Moreover, minor design changes such as moving the baffle downstream by about 10 cm can increase the flow rate by 54%. The proposed design changes can increase drying rates, improve efficiency, and reduce cycle times due to fewer obstructions in the vapor flow path. The comprehensive simulation framework combining the system-level model and the detailed CFD computations can provide a process analytical tool for more efficient and robust freeze-drying of bio-pharmaceuticals. Copyright © 2013

  2. Role of mono- and oligosaccharides from FOS as stabilizing agents during freeze-drying and storage of Lactobacillus delbrueckii subsp. bulgaricus.

    PubMed

    Romano, Nelson; Schebor, Carolina; Mobili, Pablo; Gómez-Zavaglia, Andrea

    2016-12-01

    The aim of this work was to assess the role of mono- and oligosaccharides present in fructo-oligosaccharides (FOS) mixtures as protective agents during freeze-drying and storage of Lactobacillus delbrueckii subsp. bulgaricus CIDCA 333. Different FOS mixtures were enzymatically obtained from sucrose and further purified by removing the monosaccharides produced as secondary products. Their glass transition temperatures (T g ) were determined at 11, 22 and 33% relative humidity (RH). Bacterial cultures were freeze-dried in the presence of 20% w/v solutions of the studied FOS. Their protective effect during freeze-drying was assessed by bacterial plate counting, and by determining the lag time from growth kinetics and the uptake of propidium iodide (PI). Plate counting during bacterial storage at 4°C, and 11, 22 and 33% RH for 80days completed this rational analysis of the protective effect of FOS. Purification of FOS led to an increase of T g in all the conditions assayed. Microorganisms freeze-dried in the presence of non-purified FOS were those with the shortest lag times. Bacteria freeze-dried with pure or commercial FOS (92% of total FOS) showed larger lag times (8.9-12.6h). The cultivability of microorganisms freeze-dried with non-purified FOS and with sucrose was not significantly different from that of bacteria before freeze-drying (8.74±0.14logCFU/mL). Pure or commercial FOS were less efficient in protecting bacteria during freeze-drying. All the protectants prevented membrane damage. The cultivability of bacteria freeze-dried with FOS decayed <1logarithmicunit after 80days of storage at 11% RH. When storing at 22 and 33% RH, pure and commercial FOS were those that best protected bacteria, and FOS containing monosaccharides were less efficient. The effect of FOS on bacterial protection is the result of a balance between monosaccharides, sucrose and larger FOS in the mixtures: the smallest sugars are more efficient in protecting lipid membranes, and the

  3. Comparing the acidities of aqueous, frozen, and freeze-dried phosphate buffers: Is there a "pH memory" effect?

    PubMed

    Vetráková, Ľubica; Vykoukal, Vít; Heger, Dominik

    2017-09-15

    The concept of "pH memory" has been established in the literature for the correlation between the pH of a pre-lyophilization solution and the ionization state of freeze-dried powder (lyophile). In this paper, the concept of "pH memory" is explored for the system of an aqueous solution, a frozen solution, and a lyophile. Sodium and potassium phosphate buffers in the pH range of 5-9 were frozen and lyophilized with sulfonephthalein indicators as acidity probes, and their Hammett acidity functions were compared to the initial pH of the aqueous solution. The results show that the acidities of the lyophiles are somewhat changed compared to the initial pHs, but the acidities in the frozen state differ more substantially. The Hammett acidity functions of the frozen buffers were found to be markedly dissimilar from the initial pH, especially in the sodium phosphate frozen at 233K, where an increase in the initial pH led to a decrease in the Hammett acidity function of the frozen state at a certain pH range. The large acidification observed after freezing the sodium phosphate buffer was not detected in the lyophiles after the sample had been dried; the phenomenon is explained considering the formed crystals analyzed by X-ray powder diffraction. The results suggest that monitoring the final acidity of a lyophile is not sufficient to predict all the acidity changes throughout the whole lyophilization process. The importance of well-controlled freezing and lyophilization conditions follows from the results of the research. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Bioactivity of freeze-dried platelet-rich plasma in an adsorbed form on a biodegradable polymer material.

    PubMed

    Nakajima, Yu; Kawase, Tomoyuki; Kobayashi, Mito; Okuda, Kazuhiro; Wolff, Larry F; Yoshie, Hiromasa

    2012-01-01

    Owing to the necessity for the immediate preparation from patients' blood, autologous platelet-rich plasma (PRP) limits its clinical applicability. To address this concern and respond to emergency care and other unpredictable uses, we have developed a freeze-dried PRP in an adsorbed form on a biodegradable polymer material (Polyglactin 910). On the polymer filaments of PRP mesh, which was prepared by coating the polymer mesh with human fresh PRP and subsequent freeze-drying, platelets were incorporated, and related growth factors were preserved at high levels. This new PRP mesh preparation significantly and reproducibly stimulated the proliferation of human periodontal ligament cells in vitro and neovascularization in a chorioallantoic membrane assay. A full-thickness skin defect model in a diabetic mouse demonstrated the PRP mesh, although prepared from human blood, substantially facilitated angiogenesis, granulation tissue formation, and re-epithelialization without inducing severe inflammation in vivo. These data demonstrate that our new PRP mesh preparation functions as a bioactive material to facilitate tissue repair/regeneration. Therefore, we suggest that this bioactive material, composed of allogeneic PRP, could be clinically used as a promising alternative in emergency care or at times when autologous PRP is not prepared immediately before application.

  5. Beef, chicken and lamb fatty acid analysis--a simplified direct bimethylation procedure using freeze-dried material.

    PubMed

    Lee, M R F; Tweed, J K S; Kim, E J; Scollan, N D

    2012-12-01

    When fractionation of meat lipids is not required, procedures such as saponification can be used to extract total fatty acids, reducing reliance on toxic organic compounds. However, saponification of muscle fatty acids is laborious, and requires extended heating times, and a second methylation step to convert the extracted fatty acids to fatty acid methyl esters prior to gas chromatography. Therefore the development of a more rapid direct methylation procedure would be of merit. The use of freeze-dried material for analysis is common and allows for greater homogenisation of the sample. The present study investigated the potential of using freeze-dried muscle samples and a direct bimethylation to analyse total fatty acids of meat (beef, chicken and lamb) in comparison with a saponification procedure followed by bimethylation. Both methods compared favourably for all major fatty acids measured. There was a minor difference in relation to the C18:1 trans 10 isomer with a greater (P<0.05) recovery with saponification. However, numerically the difference was small and likely as a result of approaching the limits of isomer identification by single column gas chromatography. Differences (P<0.001) between species were found for all fatty acids measured with no interaction effects. The described technique offers a simplified, quick and reliable alternative to saponification to analyse total fatty acids from muscle samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Vial freeze-drying, part 1: new insights into heat transfer characteristics of tubing and molded vials.

    PubMed

    Hibler, Susanne; Wagner, Christophe; Gieseler, Henning

    2012-03-01

    In order to optimize a freeze-drying cycle, information regarding the heat transfer characteristics of the container system is imperative. Two most recently developed tubing (TopLyo™) and molded (EasyLyo™) vial designs were compared with a standard serum tubing and molded vial, a polymer vial (TopPac™), and an amber molded EasyLyo™. In addition, the impact of methodology on the determination of reliable vial heat transfer coefficient (K(v) ) data is examined in detail. All K(v) s were gravimetrically determined by sublimation tests with pure water at 50, 100, 200, and 400 mTorr. In contrast to the traditional assumption that molded vials exhibit inefficient heat transfer characteristics, these vials showed a very similar performance compared with their serum tubing counterparts in the relevant pressure range for freeze-drying. At 100 mTorr, the TopLyo™ center vials show only 4% higher K(v) values than the EasyLyo™ center vials. All glass vials outmatch the polymer vial in terms of heat transfer, up to 30% elevated heat transfer for the TopLyo™ center vials at 400 mTorr. Sublimation tests have demonstrated to be a valuable tool to investigate the heat transfer characteristics of vials, but results are dependent on methodology. New developments in molded vial manufacturing lead to improved heat transfer performance. Copyright © 2011 Wiley Periodicals, Inc.

  7. Freeze-dried powdered yacon: effects of FOS on serum glucose, lipids and intestinal transit in the elderly.

    PubMed

    Scheid, M M A; Genaro, P S; Moreno, Y M F; Pastore, G M

    2014-10-01

    Freeze-dried powdered yacon (FDY) can be considered a prebiotic product due to its fructooligosaccharides (FOS) content. The effect of 9 weeks of daily intake of FDY containing 7.4 g of FOS on glucose, lipid metabolism and intestinal transit in a group of elderly people was investigated. Seventy-two elderly (mean age 67.11 ± 6.11) men and women were studied for 9 weeks in a double-blind, placebo-controlled experiment. They were randomly assigned to the supplement group (which received 7.4 g of FOS as FDY) or the control group. At the beginning and end of the study, anthropometric measurements, blood sampling, clinical analyses and dietary intake were assessed. A daily intake of FDY containing 7.4 g of FOS for 9 weeks was associated with a mean decrease in serum glucose (p = 0.013), but supplementation did not reduce serum lipids in the study group. The administered dose did not adversely affect intestinal transit. It did not cause bloating, flatulence or intestinal discomfort. Freeze-dried powdered yacon is a good source of FOS, and daily consumption can have a favourable effect on serum glucose in the elderly. It is also practical, easy and safe to use and store.

  8. [Preparation of freeze - drying control materials of IgG antibody against Schistosoma japonicum for immunodetection kits].

    PubMed

    Jin, Huang; Chun-Lian, Tang; Zu-Wu, Tu; Li, Tang; Ke-Hui, Zhang; Qian, Li; Jun, Ye

    2018-04-18

    To prepare freeze-drying control materials of IgG antibody against Schistosoma japonicum for detection kits. The serum samples of schistosomiasis patients from endemic areas and normal people without history of schistosome infection or contact with infested water in Hubei Province were collected. All the sera were detected by the method approved by China Food and Drug Administration and selected for preparation of quality control samples. Totally twelve positive quality control materials, ten negative quality control materials, and one sensitive and one precision quality control materials were screened. According to the positive serum level, the positive degrees of quality control materials were divided into strong, medium and weak levels. The stability could be valid for one year. The freeze-drying quality control materials of IgG antibody against S. japonicum for detection kits are prepared. They are easy to use and have good stability, and therefore, they may meet the requirement of quality control for the detection of schistosomiasis diagnostics kits.

  9. Evaluation of Different Holder Devices for Freeze-Drying in Dual-Chamber Cartridges With a Focus on Energy Transfer.

    PubMed

    Korpus, Christoph; Friess, Wolfgang

    2017-04-01

    For freeze-drying in dual-chamber cartridges, a holder device to enable handling and safe positioning in the freeze-dryer is necessary. The aim of this study was to analyze 4 different types of holder devices and to define the best system based on energy transfer. The main criteria were drying homogeneity, ability to minimize the influence of atypical radiation on product temperatures, and heat transfer effectiveness. The shell holder reduced the influence of atypical radiation by almost 60% compared to a block system and yielded the most homogenous sublimation rates. Besides the most efficient heat transfer with values of 1.58E-4 ± 2.06E-6 cal/(s*cm 2 *K) at 60 mTorr to 3.63E-4 ± 1.85E-5 cal/(s*cm 2 *K) at 200 mTorr for K tot , reaction times to shelf temperature changes were up to 4 times shorter compared to the other holder systems and even faster than for vials. The flexible holder provided a comparable shielding against atypical radiation as the shell but introduced a third barrier against energy transfer. Block and guardrail holder were the least efficient system tested. Hence, the shell holder provided the best radiation shielding, enhanced the transferability of the results to a larger scale, and improved the homogeneity between the dual-chamber cartridges. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

    PubMed

    Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

    2016-01-01

    This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

  11. Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study.

    PubMed

    Mockus, Linas N; Paul, Timothy W; Pease, Nathan A; Harper, Nancy J; Basu, Prabir K; Oslos, Elizabeth A; Sacha, Gregory A; Kuu, Wei Y; Hardwick, Lisa M; Karty, Jacquelyn J; Pikal, Michael J; Hee, Eun; Khan, Mansoor A; Nail, Steven L

    2011-01-01

    A case study has been developed to illustrate one way of incorporating a Quality by Design approach into formulation and process development for a small molecule, freeze-dried parenteral product. Sodium ethacrynate was chosen as the model compound. Principal degradation products of sodium ethacrynate result from hydrolysis of the unsaturated ketone in aqueous solution, and dimer formation from a Diels-Alder condensation in the freeze-dried solid state. When the drug crystallizes in a frozen solution, the eutectic melting temperature is above -5°C. Crystallization in the frozen system is affected by pH in the range of pH 6-8 and buffer concentration in the range of 5-50 mM, where higher pH and lower buffer concentration favor crystallization. Physical state of the drug is critical to solid state stability, given the relative instability of amorphous drug. Stability was shown to vary considerably over the ranges of pH and buffer concentration examined, and vial-to-vial variability in degree of crystallinity is a potential concern. The formulation design space was constructed in terms of pH and drug concentration, and assuming a constant 5 mM concentration of buffer. The process design space is constructed to take into account limitations on the process imposed by the product and by equipment capability.

  12. Optimisation of phenolic extraction from Averrhoa carambola pomace by response surface methodology and its microencapsulation by spray and freeze drying.

    PubMed

    Saikia, Sangeeta; Mahnot, Nikhil Kumar; Mahanta, Charu Lata

    2015-03-15

    Optimised of the extraction of polyphenol from star fruit (Averrhoa carambola) pomace using response surface methodology was carried out. Two variables viz. temperature (°C) and ethanol concentration (%) with 5 levels (-1.414, -1, 0, +1 and +1.414) were used to design the optimisation model using central composite rotatable design where, -1.414 and +1.414 refer to axial values, -1 and +1 mean factorial points and 0 refers to centre point of the design. The two variables, temperature of 40°C and ethanol concentration of 65% were the optimised conditions for the response variables of total phenolic content, ferric reducing antioxidant capacity and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. The reverse phase-high pressure liquid chromatography chromatogram of the polyphenol extract showed eight phenolic acids and ascorbic acid. The extract was then encapsulated with maltodextrin (⩽ DE 20) by spray and freeze drying methods at three different concentrations. Highest encapsulating efficiency was obtained in freeze dried encapsulates (78-97%). The obtained optimised model could be used for polyphenol extraction from star fruit pomace and microencapsulates can be incorporated in different food systems to enhance their antioxidant property. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Freeze drying formulation using microscale and design of experiment approaches: a case study using granulocyte colony-stimulating factor.

    PubMed

    Grant, Yitzchak; Matejtschuk, Paul; Bird, Christopher; Wadhwa, Meenu; Dalby, Paul A

    2012-04-01

    The lyophilization of proteins in microplates, to assess and optimise formulations rapidly, has been applied for the first time to a therapeutic protein and, in particular, one that requires a cell-based biological assay, in order to demonstrate the broader usefulness of the approach. Factorial design of experiment methods were combined with lyophilization in microplates to identify optimum formulations that stabilised granulocyte colony-stimulating factor during freeze drying. An initial screen rapidly identified key excipients and potential interactions, which was then followed by a central composite face designed optimisation experiment. Human serum albumin and Tween 20 had significant effects on maintaining protein stability. As previously, the optimum formulation was then freeze-dried in stoppered vials to verify that the microscale data is relevant to pilot scales. However, to validate the approach further, the selected formulation was also assessed for solid-state shelf-life through the use of accelerated stability studies. This approach allows for a high-throughput assessment of excipient options early on in product development, while also reducing costs in terms of time and quantity of materials required.

  14. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    PubMed

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  15. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    PubMed Central

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  16. Method for calculating the duration of vacuum drying of a metal-concrete container for spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Karyakin, Yu. E.; Nekhozhin, M. A.; Pletnev, A. A.

    2013-07-01

    A method for calculating the quantity of moisture in a metal-concrete container in the process of its charging with spent nuclear fuel is proposed. A computing method and results obtained by it for conservative estimation of the time of vacuum drying of a container charged with spent nuclear fuel by technologies with quantization and without quantization of the lower fuel element cluster are presented. It has been shown that the absence of quantization in loading spent fuel increases several times the time of vacuum drying of the metal-concrete container.

  17. On the use of tert-butanol/water cosolvent systems in production and freeze-drying of poly-ε-caprolactone nanoparticles.

    PubMed

    Zelenková, Tereza; Barresi, Antonello A; Fissore, Davide

    2015-01-01

    This work deals with the use of a water/tert-butyl alcohol (TBA) system in the manufacturing process of poly-ε-caprolactone (PCL) nanoparticles, namely in the synthesis stage, using the solvent displacement method in a confined impinging jet mixer (CIJM), and in the following freeze-drying stage. The experimental investigation evidenced that the nanoparticles size is significantly reduced with respect to the case where acetone is the solvent. Besides, the solvent evaporation step is not required before freeze-drying as TBA is fully compatible with the freeze-drying process. The effect of initial polymer concentration, flow rate, water to TBA flow rate ratio, and quench volumetric ratio on the mean nanoparticles size was investigated, and a simple equation was proposed to relate the mean nanoparticles size to these operating parameters. Then, freeze-drying of the nanoparticles suspensions was studied. Lyoprotectants (sucrose and mannitol) and steric stabilizers (Cremophor EL and Poloxamer 388) have to be used to avoid nanoparticles aggregation, thus preserving particle size distribution and mean nanoparticles size. Their effect, as well as that of the heating shelf temperature, has been investigated by means of statistical techniques, with the goal to identify which of these factors, or combination of factors, plays the key role in the nanoparticles size preservation at the end of the freeze-drying process. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. Modeling the Secondary Drying Stage of Freeze Drying: Development and Validation of an Excel-Based Model.

    PubMed

    Sahni, Ekneet K; Pikal, Michael J

    2017-03-01

    Although several mathematical models of primary drying have been developed over the years, with significant impact on the efficiency of process design, models of secondary drying have been confined to highly complex models. The simple-to-use Excel-based model developed here is, in essence, a series of steady state calculations of heat and mass transfer in the 2 halves of the dry layer where drying time is divided into a large number of time steps, where in each time step steady state conditions prevail. Water desorption isotherm and mass transfer coefficient data are required. We use the Excel "Solver" to estimate the parameters that define the mass transfer coefficient by minimizing the deviations in water content between calculation and a calibration drying experiment. This tool allows the user to input the parameters specific to the product, process, container, and equipment. Temporal variations in average moisture contents and product temperatures are outputs and are compared with experiment. We observe good agreement between experiments and calculations, generally well within experimental error, for sucrose at various concentrations, temperatures, and ice nucleation temperatures. We conclude that this model can serve as an important process development tool for process design and manufacturing problem-solving. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Investigation of PEG crystallization in frozen and freeze-dried PEGylated recombinant human growth hormone-sucrose systems: implications on storage stability.

    PubMed

    Bhatnagar, Bakul S; Martin, Susan W H; Hodge, Tamara S; Das, Tapan K; Joseph, Liji; Teagarden, Dirk L; Shalaev, Evgenyi Y; Suryanarayanan, Raj

    2011-08-01

    The objectives of the current study were to investigate (i) the phase behavior of a PEGylated recombinant human growth hormone (PEG-rhGH, ∼60 kDa) during freeze-drying and (ii) its storage stability. The phase transitions during freeze-thawing of an aqueous solution containing PEG-rhGH and sucrose were characterized by differential scanning calorimetry. Finally, PEG-rhGH and sucrose formulations containing low, medium, and high polyethylene glycol (PEG) to sucrose ratios were freeze-dried in dual-chamber syringes and stored at 4°C and 25°C. Chemical decomposition (methionine oxidation and deamidation) and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rhGH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG. Annealing caused PEG crystallization and when coupled with higher drying temperatures, the primary drying time decreased by up to 51%. When the freeze-dried cakes were stored at 4°C, while there was no change in the purity of the PEG-rhGH monomer, deamidation was highest in the formulations with the lowest PEG to sucrose ratio. When stored at 25°C, this composition also showed the most pronounced decrease in monomer purity, the highest level of aggregation, and deamidation. Furthermore, an increase in PEG crystallinity during storage was accompanied by a decrease in PEG-rhGH stability. Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability. Copyright © 2011 Wiley-Liss, Inc.

  20. Overall Quality of Fruits and Vegetables Products Affected by the Drying Processes with the Assistance of Vacuum-Microwaves.

    PubMed

    Figiel, Adam; Michalska, Anna

    2016-12-30

    The seasonality of fruits and vegetables makes it impossible to consume and use them throughout the year, thus numerous processing efforts have been made to offer an alternative to their fresh consumption and application. To prolong their availability on the market, drying has received special attention as currently this method is considered one of the most common ways for obtaining food and pharmaceutical products from natural sources. This paper demonstrates the weakness of common drying methods applied for fruits and vegetables and the possible ways to improve the quality using different drying techniques or their combination with an emphasis on the microwave energy. Particular attention has been drawn to the combined drying with the assistance of vacuum-microwaves. The quality of the dried products was ascribed by chemical properties including the content of polyphenols, antioxidant capacity and volatiles as well as physical parameters such as color, shrinkage, porosity and texture. Both these fields of quality classification were considered taking into account sensory attributes and energy aspects in the perspective of possible industrial applications. In conclusion, the most promising way for improving the quality of dried fruit and vegetable products is hybrid drying consisting of osmotic dehydration in concentrated fruit juices followed by heat pump drying and vacuum-microwave finish drying.

  1. Overall Quality of Fruits and Vegetables Products Affected by the Drying Processes with the Assistance of Vacuum-Microwaves

    PubMed Central

    Figiel, Adam; Michalska, Anna

    2016-01-01

    The seasonality of fruits and vegetables makes it impossible to consume and use them throughout the year, thus numerous processing efforts have been made to offer an alternative to their fresh consumption and application. To prolong their availability on the market, drying has received special attention as currently this method is considered one of the most common ways for obtaining food and pharmaceutical products from natural sources. This paper demonstrates the weakness of common drying methods applied for fruits and vegetables and the possible ways to improve the quality using different drying techniques or their combination with an emphasis on the microwave energy. Particular attention has been drawn to the combined drying with the assistance of vacuum-microwaves. The quality of the dried products was ascribed by chemical properties including the content of polyphenols, antioxidant capacity and volatiles as well as physical parameters such as color, shrinkage, porosity and texture. Both these fields of quality classification were considered taking into account sensory attributes and energy aspects in the perspective of possible industrial applications. In conclusion, the most promising way for improving the quality of dried fruit and vegetable products is hybrid drying consisting of osmotic dehydration in concentrated fruit juices followed by heat pump drying and vacuum-microwave finish drying. PMID:28042845

  2. The high water solubility of inclusion complex of taxifolin-γ-CD prepared and characterized by the emulsion solvent evaporation and the freeze drying combination method.

    PubMed

    Zu, Yuangang; Wu, Weiwei; Zhao, Xiuhua; Li, Yong; Zhong, Chen; Zhang, Yin

    2014-12-30

    This study selected γ-cyclodextrin (γ-CD) as the inclusion material and prepared inclusion complex of taxifolin-γ-CD by the emulsion solvent evaporation and the freeze drying combination method to achieve the improvement of the solubility and oral bioavailability of taxifolin. We selected ethyl acetate as the oil phase, deionized water as the water phase. The taxifolin emulsion was prepared using adjustable speed homogenate machine in the process of this experiment, whose particle size was related to the concentration of taxifolin solution, the volume ratio of water phase to oil phase, the speed and time of homogenate. We knew through the single-factor test that, the optimum conditions were: the concentration of taxifolin solution was 40 mg/ml, the volume ratio of water phase to oil phase was 1.5, the speed of homogenate was 5,000 rpm, the homogenate time was 11 min. Taxifolin emulsion with a MPS of 142.5 nm was obtained under the optimum conditions, then the high-concentration taxifolin solution (3mg/ml) was obtained by the rotary evaporation process. Finally, the inclusion complex of taxifolin-γ-CD was prepared by vacuum freeze-dry. The characteristics of the inclusion complex of taxifolin-γ-CD were analyzed using SEM, FTIR, XRD, DSC, and TG. The FTIR results analyzed the interaction of taxifolin and γ-CD and determined the molecular structure of the inclusion complex of taxifolin-γ-CD. The analysis results of XRD, DSC and TG indicated that the inclusion complex of taxifolin-γ-CD was obtained and showed significantly different characteristics with taxifolin. In addition, dissolving capability test, antioxidant capacity test, solvent residue test were also carried out. The experimental datas showed that the solubility of inclusion complex of taxifolin-γ-CD at 25°C and 37°C were about 18.5 times and 19.8 times of raw taxifolin, the dissolution rate of inclusion complex of taxifolin-γ-CD were about 2.84 times of raw taxifolin, the bioavailability of

  3. A comparison of freeze-drying and oven-drying preparation methods for bulk and compound-specific carbon stable isotope analyses: examples using the benthic macroinvertebrates Stenopsyche marmorata and Epeorus latifolium.

    PubMed

    Akamatsu, Fumikazu; Suzuki, Yaeko; Kato, Yoshikazu; Yoshimizu, Chikage; Tayasu, Ichiro

    2016-01-15

    Carbon stable isotope analysis of bulk samples and fatty acids is an established method for tracing carbon flow pathways and reconstructing trophic interactions, but there is no consensus on which sample drying method should be used for sample preparation. The aim of this study was to determine if freeze-drying and oven-drying treatments used to prepare samples of the benthic macroinvertebrates Stenopsyche marmorata and Epeorus latifolium for bulk and fatty-acid-specific carbon stable isotope analysis yield different isotopic ratio values. Five individuals each from two species were split in half; one half was freeze-dried and the other half was oven-dried. The samples were ground and the δ(13)C values of the bulk samples and eight fatty acids were measured following combustion using an isotope ratio mass spectrometer coupled to an elemental analyzer or gas chromatography system. The mean difference in the bulk and fatty acid δ(13)C values between freeze-dried and oven-dried samples was small (≤0.1‰ in both cases), although relatively large variations were observed in individual fatty-acid-specific δ(13)C values (maximum of ≤0.9 ‰). There were no significant differences in either bulk sample or fatty-acid-specific δ(13)C values between freeze-dried or oven-dried samples of the same species. Freeze-drying and oven-drying are equally acceptable methods for preparing freshly caught S. marmorata and E. latifolium samples for bulk and fatty-acid-specific carbon stable isotope analyses. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Effect of whey protein isolate and β-cyclodextrin wall systems on stability of microencapsulated vanillin by spray-freeze drying method.

    PubMed

    Hundre, Swetank Y; Karthik, P; Anandharamakrishnan, C

    2015-05-01

    Vanillin flavour is highly volatile in nature and due to that application in food incorporation is limited; hence microencapsulation of vanillin is an ideal technique to increase its stability and functionality. In this study, vanillin was microencapsulated for the first time by non-thermal spray-freeze-drying (SFD) technique and its stability was compared with other conventional techniques such as spray drying (SD) and freeze-drying (FD). Different wall materials like β-cyclodextrin (β-cyd), whey protein isolate (WPI) and combinations of these wall materials (β-cyd + WPI) were used to encapsulate vanillin. SFD microencapsulated vanillin with WPI showed spherical shape with numerous fine pores on the surface, which in turn exhibited good rehydration ability. On the other hand, SD powder depicted spherical shape without pores and FD encapsulated powder yielded larger particle sizes with flaky structure. FTIR analysis confirmed that there was no interaction between vanillin and wall materials. Moreover, spray-freeze-dried vanillin + WPI sample exhibited better thermal stability than spray dried and freeze-dried microencapsulated samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Stability of Staphylococcus aureus phage ISP after freeze-drying (lyophilization).

    PubMed

    Merabishvili, Maia; Vervaet, Chris; Pirnay, Jean-Paul; De Vos, Daniel; Verbeken, Gilbert; Mast, Jan; Chanishvili, Nino; Vaneechoutte, Mario

    2013-01-01

    Staphylococcus aureus phage ISP was lyophilized, using an Amsco-Finn Aqua GT4 freeze dryer, in the presence of six different stabilizers at different concentrations. Stability of the lyophilized phage at 4 °C was monitored up to 37 months and compared to stability in Luria Bertani broth and physiological saline at 4 °C. Sucrose and trehalose were shown to be the best stabilizing additives, causing a decrease of only 1 log immediately after the lyophilization procedure and showing high stability during a 27 month storage period.

  6. The performance of five fruit-derived and freeze-dried potentially probiotic Lactobacillus strains in apple, orange and grape juices.

    PubMed

    Garcia, Estefânia Fernandes; de Oliveira Araújo, Amanda; Luciano, Winnie Alencar; de Albuquerque, Thatyane Mariano Rodrigues; de Oliveira Arcanjo, Narciza Maria; Madruga, Marta Suely; Dos Santos Lima, Marcos; Magnani, Marciane; Saarela, Maria; de Souza, Evandro Leite

    2018-03-30

    This study assessed the survival of the fruit-derived and freeze-dried L. plantarum 49, L. brevis 59, L. paracasei 108, L. fermentum 111 and L. pentosus 129 strains during frozen storage and when incorporated into apple, orange and grape juice stored under refrigeration. Physicochemical parameters of juices containing the freeze-dried Lactobacillus strains and the survival of the test strains in the fruit juices during in vitro digestion were also evaluated. No decreases in survival rates (log N/log N0) of the freeze-dried cells were observed up to 1 month of storage. The survival rates of the freeze-dried strains L. plantarum 49 and L. paracasei 108 were >0.75 up to 4 months of storage. All freeze-dried strains exhibited survival rates of >0.75 up to 2 weeks of storage in apple juice; only L. plantarum 49 and L. paracasei 108 showed similar survival rates in orange and grape juices up to 2 weeks of storage. The contents of the monitored organic acids or sugars during storage varied depending on the added strain and the type of fruit juice. At the end of the in vitro digestion, L. brevis 59, L. paracasei 108 and L. fermentum 111 showed survival rates of >0.80 in apple juice. Apple juice was as the best substrate to the survival of the tested freeze-dried Lactobacillus strains over time. L. paracasei 108 and L. plantarum 49 as the strains presenting the best performance for incorporation in potentially probiotic fruit juices. This article is protected by copyright. All rights reserved.

  7. Aseptic Freeze-Dried versus Sterile Wet-Packaged Human Cadaveric Acellular Dermal Matrix in Immediate Tissue Expander Breast Reconstruction: A Propensity Score Analysis.

    PubMed

    Hanson, Summer E; Meaike, Jesse D; Selber, Jesse C; Liu, Jun; Li, Liang; Hassid, Victor J; Baumann, Donald P; Butler, Charles E; Garvey, Patrick B

    2018-05-01

    Although multiple acellular dermal matrix sources exist, it is unclear how its processing impacts complication rates. The authors compared complications between two preparations of human cadaveric acellular dermal matrix (freeze dried and ready-to-use) in immediate tissue expander breast reconstruction to analyze the effect of processing on complications. The authors retrospectively reviewed all alloplastic breast reconstructions with freeze-dried or ready-to-use human acellular dermal matrices between 2006 and 2016. The primary outcome measure was surgical-site occurrence defined as seroma, skin dehiscence, surgical-site infection, or reconstruction failure. The two groups were compared before and after propensity score matching. The authors included 988 reconstructions (freeze-dried, 53.8 percent; ready-to-use, 46.2 percent). Analysis of 384 propensity score-matched pairs demonstrated a slightly higher rate of surgical-site occurrence (21.4 percent versus 16.7 percent; p = 0.10) and surgical-site infection (9.6 percent versus 7.8 percent; p = 0.13) in the freeze-dried group than in the ready-to-use group, but the difference was not significant. However, failure was significantly higher for the freeze-dried versus ready-to-use group (7.8 percent versus 4.4 percent; p = 0.050). This is the largest study comparing the outcomes of alloplastic breast reconstruction using human acellular dermal matrix materials prepared by different methods. The authors demonstrated higher early complications with aseptic, freeze-dried matrix than with sterile ready-to-use matrix; reconstructive failure was the only outcome to achieve statistical significance. The authors conclude that acellular dermal matrix preparation has an independent impact on patient outcomes in their comparison of one company's product. Therapeutic, III.

  8. Characterization of biomasses, concentrates, and permeates of dried powder of Kombucha fermentation of spinach (Amaranthus sp.) and broccoli (Brassica oleracea) with membrane microfiltration and freeze drying techniques for natural sources of folic acid

    NASA Astrophysics Data System (ADS)

    Nugraha, Tutun; Susilowati, Agustine; Aspiyanto, Lotulung, Puspa Dewi; Maryati, Yati

    2017-11-01

    Fermentation of spinach (Amaranthus sp) and Broccoli (Brassica oleracea) using Kombucha Culture has been shown to produce biomass that has the potential to become natural sources of folic acid. To produce the materials, following the fermentation, the biomass was filtered using membrane microfiltration (0.15 µm) at a pressure of 40 psia, at room temperature, yielding the concentrate and the permeate fractions. Following this step, freeze drying process was done on the biomass feeds, as well as on the concentrate and permeate fractions. For the freeze drying stage, the samples were frozen, and the condenser was kept at -50°C for 40 hours, while the pressure in the chamber was set at 200 Pa. Freeze drying results showed that the final products, have differences in compositions, as well as differences in the dominat monomers of folates. After water content was driven out, freeze drying increased the concentrations of folic acid in the dried products, and was found to be the highest in the concentrate fractions. Freeze drying has been shown to be capable of protecting the folates from heat and oxidative damages that typicaly occur with other types of drying. The final freeze dried concentrates of fermentation of spinach and broccoli were found to contain folic acid at 2531.88 µg/mL and 1626.94 µg/mL, total solids at 87.23% and 88.65 %, total sugar at 22.66 µg/mL and 25.13 µg/mL, total reducing sugar at 34.46 mg/mL and 15.22 mg/mL, as well as disolved protein concentrations at 0.93 mg/mL and 1.45 mg/mL. Liquid Chromatography Mass Spectometry (LC-MS) identification of the folates in the freeze dried concentrates of fermented spinach and broccoli was done using folic acid and glutamic acid standard solutions as the reference materials. The results showed the presence of folic acid and showed that the dominant monomers of molecules of folates with molecular weights of 441.44 Da. and 441.54 Da. for spinach and broccoli respectively. Moreover, the monomers of glutamic

  9. Effects of long-term simulated martian conditions on a freeze-dried and homogenized bacterial permafrost community.

    PubMed

    Hansen, Aviaja A; Jensen, Lars L; Kristoffersen, Tommy; Mikkelsen, Karina; Merrison, Jonathan; Finster, Kai W; Lomstein, Bente Aa

    2009-03-01

    Indigenous bacteria and biomolecules (DNA and proteins) in a freeze-dried and homogenized Arctic permafrost were exposed to simulated martian conditions that correspond to about 80 days on the surface of Mars with respect to the accumulated UV dose. The simulation conditions included UV radiation, freeze-thaw cycles, the atmospheric gas composition, and pressure. The homogenized permafrost cores were subjected to repeated cycles of UV radiation for 3 h followed by 27 h without irradiation. The effects of the simulation conditions on the concentrations of biomolecules; numbers of viable, dead, and cultured bacteria; as well as the community structure were determined. Simulated martian conditions resulted in a significant reduction of the concentrations of DNA and amino acids in the uppermost 1.5 mm of the soil core. The total number of bacterial cells was reduced in the upper 9 mm of the soil core, while the number of viable cells was reduced in the upper 15 mm. The number of cultured aerobic bacteria was reduced in the upper 6 mm of the soil core, whereas the community structure of cultured anaerobic bacteria was relatively unaffected by the exposure conditions. As explanations for the observed changes, we propose three causes that might have been working on the biological material either individually or synergistically: (i) UV radiation, (ii) UV-generated reactive oxygen species, and (iii) freeze-thaw cycles. Currently, the production and action of reactive gases is only hypothetical and will be a central subject in future investigations. Overall, we conclude that in a stable environment (no wind-/pressure-induced mixing) biological material is efficiently shielded by a 2 cm thick layer of dust, while it is relatively rapidly destroyed in the surface layer, and that biomolecules like proteins and polynucleotides are more resistant to destruction than living biota.

  10. Effects of Long-Term Simulated Martian Conditions on a Freeze-Dried and Homogenized Bacterial Permafrost Community

    NASA Astrophysics Data System (ADS)

    Hansen, Aviaja A.; Jenson, Lars L.; Kristoffersen, Tommy; Mikkelsen, Karina; Merrison, Jonathan; Finster, Kai W.; Lomstein, Bente Aa.

    2009-03-01

    Indigenous bacteria and biomolecules (DNA and proteins) in a freeze-dried and homogenized Arctic permafrost were exposed to simulated martian conditions that correspond to about 80 days on the surface of Mars with respect to the accumulated UV dose. The simulation conditions included UV radiation, freeze-thaw cycles, the atmospheric gas composition, and pressure. The homogenized permafrost cores were subjected to repeated cycles of UV radiation for 3 h followed by 27 h without irradiation. The effects of the simulation conditions on the concentrations of biomolecules; numbers of viable, dead, and cultured bacteria; as well as the community structure were determined. Simulated martian conditions resulted in a significant reduction of the concentrations of DNA and amino acids in the uppermost 1.5 mm of the soil core. The total number of bacterial cells was reduced in the upper 9 mm of the soil core, while the number of viable cells was reduced in the upper 15 mm. The number of cultured aerobic bacteria was reduced in the upper 6 mm of the soil core, whereas the community structure of cultured anaerobic bacteria was relatively unaffected by the exposure conditions. As explanations for the observed changes, we propose three causes that might have been working on the biological material either individually or synergistically: (i) UV radiation, (ii) UV-generated reactive oxygen species, and (iii) freeze-thaw cycles. Currently, the production and action of reactive gases is only hypothetical and will be a central subject in future investigations. Overall, we conclude that in a stable environment (no wind-/pressure-induced mixing) biological material is efficiently shielded by a 2 cm thick layer of dust, while it is relatively rapidly destroyed in the surface layer, and that biomolecules like proteins and polynucleotides are more resistant to destruction than living biota.

  11. Comparison of blueberry powder produced via foam-mat freeze-drying versus spray-drying: evaluation of foam and powder properties.

    PubMed

    Darniadi, Sandi; Ho, Peter; Murray, Brent S

    2018-03-01

    Blueberry juice powder was developed via foam-mat freeze-drying (FMFD) and spray-drying (SD) via addition of maltodextrin (MD) and whey protein isolate (WPI) at weight ratios of MD/WPI = 0.4 to 3.2 (with a fixed solids content of 5 wt% for FMFD and 10 wt% for SD). Feed rates of 180 and 360 mL h -1 were tested in SD. The objective was to evaluate the effect of the drying methods and carrier agents on the physical properties of the corresponding blueberry powders and reconstituted products. Ratios of MD/WPI = 0.4, 1.0 and 1.6 produced highly stable foams most suitable for FMFD. FMFD gave high yields and low bulk density powders with flake-like particles of large size that were also dark purple with high red values. SD gave low powder recoveries. The powders had higher bulk density and faster rehydration times, consisting of smooth, spherical and smaller particles than in FMFD powders. The SD powders were bright purple but less red than FMFD powders. Solubility was greater than 95% for both FMFD and SD powders. The FMFD method is a feasible method of producing blueberry juice powder and gives products retaining more characteristics of the original juice than SD. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Effect of oven drying and freeze drying on the antioxidant and functional properties of protein hydrolysates derived from freshwater fish (Cirrhinus mrigala) using papain enzyme.

    PubMed

    Elavarasan, Krishnamoorthy; Shamasundar, Bangalore Aswathnarayan

    2016-02-01

    Fish protein hydrolysate (FPH) was prepared from fresh water fish Cirrhinus mrigala using papain and dried in oven (OD-FPH) and freeze dryer (FD-FPH). The electron micrographs of FD-FPH samples showed porous structure. The browning intensity of OD-FPH samples was higher than the FD-FPH samples. The DPPH (2, 2 Diphenyl-1-picrylhydrazyl) free radical scavenging activity and linoleic acid peroxidation inhibition activity of FPH were not affected by oven drying process. The sequential digestion of FPH with pepsin and pancreatin reduced the antioxidant properties in both OD-FPH and FD-FPH samples. The solubility of proteins in OD-FPH was lower at pH 5 while for that of FD-FPH it was at pH 7 with water as solvent. The surface active properties of FD-FPH samples were higher than OD-FPH samples. The oven drying of fish protein hydrolysates may be advocated considering the properties and cost of production.

  13. CFD simulation of a dry scroll vacuum pump with clearances, solid heating and thermal deformation

    NASA Astrophysics Data System (ADS)

    Spille-Kohoff, A.; Hesse, J.; Andres, R.; Hetze, F.

    2017-08-01

    Although dry scroll vacuum pumps (DSPV) are essential devices in many different industrial processes, the CFD simulation of such pumps is not widely used and often restricted to simplified cases due to its complexity: The working principle with a fixed and an orbiting scroll leads to working chambers that are changing in time and are connected through moving small radial and axial clearances in the range of 10 to 100 μm. Due to the low densities and low mass flow rates in vacuum pumps, it is important to include heat transfer towards and inside the solid components. Solid heating is very slow compared to the scroll revolution speed and the gas behaviour, thus a special workflow is necessary to reach the working conditions in reasonable simulation times. The resulting solid temperature is then used to compute the thermal deformation, which usually results in gap size changes that influence leakage flows. In this paper, setup steps and results for the simulation of a DSVP are shown and compared to theoretical and experimental results. The time-varying working chambers are meshed with TwinMesh, a hexahedral meshing programme for positive displacement machines. The CFD simulation with ANSYS CFX accounts for gas flow with compressibility and turbulence effects, conjugate heat transfer between gas and solids, and leakage flows through the clearances. Time-resolved results for torques, chamber pressure, mass flow, and heat flow between gas and solids are shown, as well as time- and space-resolved results for pressure, velocity, and temperature for different operating conditions of the DSVP.

  14. Microbiological quality and biogenic amines in ready-to-eat grilled chicken fillets under vacuum packing, freezing, and high-dose irradiation.

    PubMed

    Baptista, R F; Lemos, M; Teixeira, C E; Vital, H C; Carneiro, C S; Mársico, E T; Conte Júnior, C A; Mano, S B

    2014-06-01

    The combined effects of cooking, vacuum packing, freezing, and high-dose gamma irradiation in the microbiological conservation and in biogenic amine (BA) contents of ready-to-eat grilled breast chicken fillets are investigated in this work. After seasoning, cooking, and vacuum packing, one-third of the samples were stored at -25°C (T1). The remaining two-thirds were treated with 48 kGy, one-third being stored at -25°C (T2) and the other one-third kept at room temperature (T3). All samples were periodically analyzed to determine growth of heterotrophic aerobic mesophilic bacteria (HAMB) and levels of BA (tyramine, TYM; putrescine, PUT; cadaverine, CAD; spermidine, SPD; histamine, HYM; and spermine, SPM). Variance analysis was performed to determine significant changes in the measured data. Grilling caused HAMB counts in seasoned samples to drop from 5.3 log cfu/g to zero. In addition, no viable HAMB cells were detected in the samples throughout the 12-mo storage time. Regarding the BA analyses, the highest mean levels were measured for SPM and CAD with significantly higher levels (P < 0.05) being determined in nonirradiated samples (T1). Furthermore, significantly lower mean levels for the total content of BA were observed in the irradiated samples. Relative to T1 (7.5 ± 1.5 mg/kg), the figures were 47 ± 23% for T2 and 60 ± 25% for T3, mostly due to loss of CAD by radiolysis. Therefore, it can be concluded that the combination of grilling, vacuum packing, freezing, and high-dose gamma irradiation efficiently eliminated HAMB, while sustaining acceptable levels of BA in ready-to-eat chicken breast fillets throughout the 12 mo of storage at room temperature. Poultry Science Association Inc.

  15. Healthy offspring from freeze-dried mouse spermatozoa held on the International Space Station for 9 months.

    PubMed

    Wakayama, Sayaka; Kamada, Yuko; Yamanaka, Kaori; Kohda, Takashi; Suzuki, Hiromi; Shimazu, Toru; Tada, Motoki N; Osada, Ikuko; Nagamatsu, Aiko; Kamimura, Satoshi; Nagatomo, Hiroaki; Mizutani, Eiji; Ishino, Fumitoshi; Yano, Sachiko; Wakayama, Teruhiko

    2017-06-06

    If humans ever start to live permanently in space, assisted reproductive technology using preserved spermatozoa will be important for producing offspring; however, radiation on the International Space Station (ISS) is more than 100 times stronger than that on Earth, and irradiation causes DNA damage in cells and gametes. Here we examined the effect of space radiation on freeze-dried mouse spermatozoa held on the ISS for 9 mo at -95 °C, with launch and recovery at room temperature. DNA damage to the spermatozoa and male pronuclei was slightly increased, but the fertilization and birth rates were similar to those of controls. Next-generation sequencing showed only minor genomic differences between offspring derived from space-preserved spermatozoa and controls, and all offspring grew to adulthood and had normal fertility. Thus, we demonstrate that although space radiation can damage sperm DNA, it does not affect the production of viable offspring after at least 9 mo of storage on the ISS.

  16. Angular absorption of light used for evaluation of structural damage to porcine meat caused by aging, drying and freezing.

    PubMed

    Kaspar, Pavel; Prokopyeva, Elena; Tománek, Pavel; Grmela, Lubomír

    2017-04-01

    Meat as a rich source of protein is sought after by people from all over the world. It is also very susceptible to decay because of many internal and external processes affecting it. In this work an easy and quick method of detection of structural damage caused by decay or mishandling the meat is attempted by the method of angular absorption of light. The difference between structural changes due to aging, drying and freezing is explored and the resulting changes in light absorption in meat samples are presented. This work demonstrates that the measurement of optical angular dependency of absorption in relation to the muscle fibers in muscle tissue has the potential of detecting structural damage to the sample for meat quality control purposes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.

    PubMed

    Staley, Christopher; Vaughn, Byron P; Graiziger, Carolyn T; Singroy, Stephanie; Hamilton, Matthew J; Yao, Dan; Chen, Chi; Khoruts, Alexander; Sadowsky, Michael J

    2017-05-04

    Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.

  18. Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study

    PubMed Central

    Staley, Christopher; Hamilton, Matthew J.; Vaughn, Byron P.; Graiziger, Carolyn T.; Newman, Krista M.; Kabage, Amanda J.; Sadowsky, Michael J.; Khoruts, Alexander

    2017-01-01

    OBJECTIVES Fecal microbiota transplantation (FMT) is increasingly being used for treatment of recurrent Clostridium difficile infection (R-CDI) that cannot be cured with antibiotics alone. In addition, FMT is being investigated for a variety of indications where restoration or restructuring of the gut microbial community is hypothesized to be beneficial. We sought to develop a stable, freeze-dried encapsulated preparation of standardized fecal microbiota that can be used for FMT with ease and convenience in clinical practice and research. METHODS We systematically developed a lyophilization protocol that preserved the viability of bacteria across the taxonomic spectrum found in fecal microbiota and yielded physicochemical properties that enabled consistent encapsulation. We also treated a cohort of R-CDI patients with a range of doses of encapsulated microbiota and analyzed the associated changes in the fecal microbiome of the recipients. RESULTS The optimized lyophilized preparation satisfied all our preset goals for physicochemical properties, encapsulation ease, stability at different temperatures, and microbiota viability in vitro and in vivo (germ-free mice). The capsule treatment was administered to 49 patients. Overall, 43/49 (88%) of patients achieved a clinical success, defined as no recurrence of CDI over 2 months. Analysis of the fecal microbiome demonstrated near normalization of the fecal microbial community by 1 month following FMT treatment. The simplest protocol using the lowest dose (2.1–2.5×1011 bacteria in 2–3 capsules) without any colon purgative performed equally well in terms of clinical outcomes and microbiota engraftment. CONCLUSIONS A single administration of encapsulated, freeze-dried fecal microbiota from a healthy donor was highly successful in treating antibiotic-refractory R-CDI syndrome. PMID:28195180

  19. Spray-freeze-drying of nanosuspensions: the manufacture of insulin particles for needle-free ballistic powder delivery

    PubMed Central

    Schiffter, Heiko; Condliffe, Jamie; Vonhoff, Sebastian

    2010-01-01

    The feasibility of preparing microparticles with high insulin loading suitable for needle-free ballistic drug delivery by spray-freeze-drying (SFD) was examined in this study. The aim was to manufacture dense, robust particles with a diameter of around 50 µm, a narrow size distribution and a high content of insulin. Atomization using ultrasound atomizers showed improved handling of small liquid quantities as well as narrower droplet size distributions over conventional two-fluid nozzle atomization. Insulin nanoparticles were produced by SFD from solutions with a low solid content (<10 mg ml−1) and subsequent ultra-turrax homogenization. To prepare particles for needle-free ballistic injection, the insulin nanoparticles were suspended in matrix formulations with a high excipient content (>300 mg ml−1) consisting of trehalose, mannitol, dextran (10 kDa) and dextran (150 kDa) (abbreviated to TMDD) in order to maximize particle robustness and density after SFD. With the increase in insulin content, the viscosity of the nanosuspensions increased. Liquid atomization was possible up to a maximum of 250 mg of nano-insulin suspended in a 1.0 g matrix. However, if a narrow size distribution with a good correlation between theoretical and measurable insulin content was desired, no more than 150 mg nano-insulin could be suspended per gram of matrix formulation. Particles were examined by laser light diffraction, scanning electron microscopy and tap density testing. Insulin stability was assessed using size exclusion chromatography (SEC), reverse phase chromatography and Fourier transform infrared (FTIR) spectroscopy. Densification of the particles could be achieved during primary drying if the product temperature (Tprod) exceeded the glass transition temperature of the freeze concentrate (Tg′) of −29.4°C for TMDD (3∶3∶3∶1) formulations. Particles showed a collapsed and wrinkled morphology owing to viscous flow of the freeze concentrate. With increasing insulin

  20. Rapid high throughput amylose determination in freeze dried potato tuber samples

    Approximately 80% of the fresh weight of a potato tuber is water; nearly all of the remaining dry matter is starch. Most of the starch (70%) is composed of amylopectin, while the remainder is amylose. The ratio between amylose and amylopectin is the most important property influencing the physical p...

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

    PubMed

    Chen, Xiaodong; Sadineni, Vikram; Maity, Mita; Quan, Yong; Enterline, Matthew; Mantri, Rao V

    2015-12-01

    Lyophilization is an approach commonly undertaken to formulate drugs that are unstable to be commercialized as ready to use (RTU) solutions. One of the important aspects of commercializing a lyophilized product is to transfer the process parameters that are developed in lab scale lyophilizer to commercial scale without a loss in product quality. This process is often accomplished by costly engineering runs or through an iterative process at the commercial scale. Here, we are highlighting a combination of computational and experimental approach to predict commercial process parameters for the primary drying phase of lyophilization. Heat and mass transfer coefficients are determined experimentally either by manometric temperature measurement (MTM) or sublimation tests and used as inputs for the finite element model (FEM)-based software called PASSAGE, which computes various primary drying parameters such as primary drying time and product temperature. The heat and mass transfer coefficients will vary at different lyophilization scales; hence, we present an approach to use appropriate factors while scaling-up from lab scale to commercial scale. As a result, one can predict commercial scale primary drying time based on these parameters. Additionally, the model-based approach presented in this study provides a process to monitor pharmaceutical product robustness and accidental process deviations during Lyophilization to support commercial supply chain continuity. The approach presented here provides a robust lyophilization scale-up strategy; and because of the simple and minimalistic approach, it will also be less capital intensive path with minimal use of expensive drug substance/active material.

  2. Moisture Sorption and Thermodynamic Properties of Vacuum-Dried Capsosiphon fulvescens Powder

    PubMed Central

    Zuo, Li; Rhim, Jong-Whan; Lee, Jun Ho

    2015-01-01

    The moisture sorption isotherms of vacuum-dried edible green alga (Capsosiphon fulvescens) powders were determined at 25, 35, and 45°C and water activity (aw) in the range of 0.11~0.94. An inversion effect of temperature was found at high water activity (>0.75). Various mathematical models were fitted to the experimental data, and Brunauer, Emmett, and Teller model was found to be the most suitable model describing the relationship between equilibrium moisture content and water activity (<0.45). Henderson model could also provide excellent agreement between the experimental and predicted values despite of the intersection point. Net isosteric heat of adsorption decreased from 15.77 to 9.08 kJ/mol with an increase in equilibrium moisture content from 0.055 to 0.090 kg H2O/kg solids. The isokinetic temperature (Tβ) was 434.79 K, at which all the adsorption reactions took place at the same rate. The enthalpy-entropy compensation suggested that the mechanism of the adsorption process was shown to be enthalpy-driven. PMID:26451360

  3. Antioxidant and anti-inflammatory activities of freeze-dried grapefruit phenolics as affected by gum arabic and bamboo fibre addition and microwave pretreatment.

    PubMed

    García-Martínez, Eva; Andújar, Isabel; Yuste Del Carmen, Alberto; Prohens, Jaime; Martínez-Navarrete, Nuria

    2018-06-01

    Recent epidemiological studies have suggested that phenolic compounds present in grapefruit play an important role in the bioactive properties of this fruit. However, the consumption of fresh grapefruit is low. Freeze-dried powdered grapefruit can be an alternative to promote this fruit consumption. To improve the quality and stability of the powdered fruit, encapsulating and anticaking agents can be added. In the present study, different grapefruit powders obtained by freeze-drying with the addition of gum arabic (1.27 g per 100 g) and bamboo fibre (0.76 g per 100 g) with and without a pre-drying microwave treatment were compared with the fresh and freeze-dried fruit with no carriers added, aiming to evaluate the effect of these preservation processes on phenolics content and on its antioxidant [1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing ability of plasma (FRAP)] and anti-inflamatory (evaluated in RAW 264.7 macrophages) capacities. Freeze-drying and gum arabic and bamboo fibre addition significantly increased total phenolics, as well as the antioxidant and anti-inflammatory activities (by inhibiting nitric oxide production of lipopolysaccharide activated RAW 264.7 macrophages), of grapefruit. An additional increase in these parameters was obtained with microwave pretreatment before freeze-drying. The combined addition of gum arabic and bamboo fibre to grapefruit puree and the application of a microwave pretreatment improve the functional properties of the fruit without showing cytotoxicity in vitro. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. A GIS analysis of the relationship between sinkholes, dry-well complaints and groundwater pumping for frost-freeze protection of winter strawberry production in Florida.

    PubMed

    Aurit, Mark D; Peterson, Robert O; Blanford, Justine I

    2013-01-01

    Florida is riddled with sinkholes due to its karst topography. Sometimes these sinkholes can cause extensive damage to infrastructure and homes. It has been suggested that agricultural practices, such as sprinkler irrigation methods used to protect crops, can increase the development of sinkholes, particularly when temperatures drop below freezing, causing groundwater levels to drop quickly during groundwater pumping. In the strawberry growing region, Dover/Plant City, Florida, the effects have caused water shortages resulting in dry-wells and ground subsidence through the development of sinkholes that can be costly to maintain and repair. In this study, we look at how frost-freeze events have affected West Central Florida over the past 25 years with detailed comparisons made between two cold-years (with severe frost-freeze events) and a warm year (no frost-freeze events). We analyzed the spatial and temporal correlation between strawberry farming freeze protection practices and the development of sinkholes/dry well complaints, and assessed the economic impact of such events from a water management perspective by evaluating the cost of repairing and drilling new wells and how these compared with using alternative crop-protection methods. We found that the spatial distribution of sinkholes was non-random during both frost-freeze events. A strong correlation between sinkhole occurrence and water extraction and minimum temperatures was found. Furthermore as temperatures fall below 41°F and water levels decrease by more than 20 ft, the number of sinkholes increase greatly (N >10). At this time alternative protection methods such as freeze-cloth are cost prohibitive in comparison to repairing dry wells. In conclusion, the findings from this study are applicable in other agricultural areas and can be used to develop comprehensive water management plans in areas where the abstraction of large quantities of water occur.

  5. A GIS Analysis of the Relationship between Sinkholes, Dry-Well Complaints and Groundwater Pumping for Frost-Freeze Protection of Winter Strawberry Production in Florida

    PubMed Central

    Aurit, Mark D.; Peterson, Robert O.; Blanford, Justine I.

    2013-01-01

    Florida is riddled with sinkholes due to its karst topography. Sometimes these sinkholes can cause extensive damage to infrastructure and homes. It has been suggested that agricultural practices, such as sprinkler irrigation methods used to protect crops, can increase the development of sinkholes, particularly when temperatures drop below freezing, causing groundwater levels to drop quickly during groundwater pumping. In the strawberry growing region, Dover/Plant City, Florida, the effects have caused water shortages resulting in dry- wells and ground subsidence through the development of sinkholes that can be costly to maintain and repair. In this study, we look at how frost-freeze events have affected West Central Florida over the past 25 years with detailed comparisons made between two cold-years (with severe frost-freeze events) and a warm year (no frost-freeze events). We analyzed the spatial and temporal correlation between strawberry farming freeze protection practices and the development of sinkholes/dry well complaints, and assessed the economic impact of such events from a water management perspective by evaluating the cost of repairing and drilling new wells and how these compared with using alternative crop-protection methods. We found that the spatial distribution of sinkholes was non-random during both frost-freeze events. A strong correlation between sinkhole occurrence and water extraction and minimum temperatures was found. Furthermore as temperatures fall below 41°F and water levels decrease by more than 20 ft, the number of sinkholes increase greatly (N >10). At this time alternative protection methods such as freeze-cloth are cost prohibitive in comparison to repairing dry wells. In conclusion, the findings from this study are applicable in other agricultural areas and can be used to develop comprehensive water management plans in areas where the abstraction of large quantities of water occur. PMID:23326518

  6. Application of the freeze-dried bioluminescent bioreporter Pseudomonas putida mt-2 KG1206 to the biomonitoring of groundwater samples from monitoring wells near gasoline leakage sites.

    PubMed

    Ko, Kyung-Seok; Kong, In Chul

    2017-02-01

    This study examined the applicability of a freeze-dried bioluminescent bioreporter, Pseudomonas putida mt-2 KG1206 (called KG1206), to the biomonitoring of groundwater samples. Samples were collected from the monitoring wells of gas station tanks or old pipeline leakage sites in Korea. In general, the freeze-dried strain in the presence of pure inducer chemicals showed low bioluminescence activity and a different activity order compared with that of the subcultured strain. The effects of KNO 3 as a bioluminescence stimulant were observed on the pure inducers and groundwater samples. The stimulation rates varied according to the type of inducers and samples, ranging from 2.2 to 20.5 times (for pure inducers) and from 1.1 to 11 times (for groundwater samples) the total bioluminescence of the control. No considerable correlations were observed between the bioluminescence intensity of the freeze-dried strain and the inducer concentrations in the samples (R 2  < 0.1344). However, samples without a high methyl tertiary butyl ether (MTBE) level and those from the gas station leakage site showed reasonable correlations with the bioluminescence activity with R 2 values of 0.3551 and 0.4131, respectively. These results highlight the potential of using freeze-dried bioluminescent bacteria as a rapid, simple, and portable tool for the preliminary biomonitoring of specific pollutants at contaminated sites.

  7. Development of Biomimetic Hybrid Porous Scaffold of Chitosan/Polyvinyl Alcohol/Carboxymethyl Cellulose by Freeze-Dried and Salt Leached Technique.

    PubMed

    Kanimozhi, K; Basha, S Khaleel; Kumari, V Sugantha; Kaviyarasu, K

    2018-07-01

    Freeze drying and salt leaching methods were applied to fabricate Chitosan/Poly(vinyl alcohol)/Carboxymethyl cellulose (CPCMC) biomimetic porous scaffolds for soft tissue engineering. The properties of these scaffolds were investigated and compared to those by freeze drying and salt leaching methods respectively. The salt-leached CS/PVA/CMC scaffolds were easily formed into desired shapes with a uniformly distributed and interconnected pore structure with an average pore size. The mechanical strength of the scaffolds increased with the porosity, and were easily modulated by the addition of carboxymethyl cellulose. The morphology of the porous scaffolds observed using a SEM exhibited good porosity and interconnectivity of pores. MTT assay using L929 fibroblast cells demonstrated that the cell viability of the porous scaffold was good. Scaffolds prepared by salt leached method show larger swelling capacity, and mechanical strength, potent antibacterial activity and more cell viability than freeze dried method. It is found that salt leaching method has distinguished characteristics of simple, efficient, feasible and less economic than freeze dried scaffolds.

  8. Robustness testing in pharmaceutical freeze-drying: inter-relation of process conditions and product quality attributes studied for a vaccine formulation.

    PubMed

    Schneid, Stefan C; Stärtzel, Peter M; Lettner, Patrick; Gieseler, Henning

    2011-01-01

    The recent US Food and Drug Administration (FDA) legislation has introduced the evaluation of the Design Space of critical process parameters in manufacturing processes. In freeze-drying, a "formulation" is expected to be robust when minor deviations of the product temperature do not negatively affect the final product quality attributes. To evaluate "formulation" robustness by investigating the effect of elevated product temperature on product quality using a bacterial vaccine solution. The vaccine solution was characterized by freeze-dry microscopy to determine the critical formulation temperature. A conservative cycle was developed using the SMART™ mode of a Lyostar II freeze dryer. Product temperature was elevated to imitate intermediate and aggressive cycle conditions. The final product was analyzed using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), Karl Fischer, and modulated differential scanning calorimetry (MDSC), and the life cell count (LCC) during accelerated stability testing. The cakes processed at intermediate and aggressive conditions displayed larger pores with microcollapse of walls and stronger loss in LCC than the conservatively processed product, especially during stability testing. For all process conditions, a loss of the majority of cells was observed during storage. For freeze-drying of life bacterial vaccine solutions, the product temperature profile during primary drying appeared to be inter-related to product quality attributes.

  9. Effects of protectant and rehydration conditions on the survival rate and malolactic fermentation efficiency of freeze-dried Lactobacillus plantarum JH287.

    PubMed

    Lee, Sae-Byuk; Kim, Dong-Hwan; Park, Heui-Dong

    2016-09-01

    In this study, Lactobacillus plantarum JH287 was used as a malolactic fermentation starter in Campbell Early wine production. L. plantarum JH287 was first lyophilized, and the malolactic fermentation potential of freeze-dried L. plantarum JH287 was investigated. Different protective media and rehydration conditions were tested to improve the survival rate of freeze-dried L. plantarum JH287. Optimal protective medium contained 10 % sorbitol and 10 % skim milk. The optimal rehydration condition was a 1-h rehydration time conducted in the same protective media, and the combination of these two methods produced a survival rate of 86.37 %. In addition, a 77.71 % survival rate was achieved using freeze-dried samples that were stored at 4 °C for 2 months. Freeze-dried L. plantarum JH287 and Saccharomyces cerevisiae Fermivin were used to inoculate the Campbell Early grape must to decrease its malic acid content. Using this mixed-fermentation method, wine showed a decrease in malic acid content after 9 days of fermentation. GC-MS analysis detected 15 volatile ester compounds in the wine. A sensory evaluation showed that the taste and aroma of mix-fermented wine were better than those of the control that had not been inoculated with L. plantarum JH287.

  10. Effect of controlled ice nucleation on primary drying stage and protein recovery in vials cooled in a modified freeze-dryer.

    PubMed

    Passot, Stéphanie; Tréléa, Ioan Cristian; Marin, Michèle; Galan, Miquel; Morris, G John; Fonseca, Fernanda

    2009-07-01

    The freezing step influences lyophilization efficiency and protein stability. The main objective of this work was to investigate the impact on the primary drying stage of an ultrasound controlled ice nucleation technology, compared with usual freezing protocols. Lyophilization cycles involving different freezing protocols (applying a constant shelf cooling rate of 1 degrees C/min or 0.2 degrees C/min, putting vials on a precooled shelf, and controlling nucleation by ultrasounds or by addition of a nucleating agent) were performed in a prototype freeze-dryer. Three protective media including sucrose or maltodextrin and differing by their thermal properties and their ability to preserve a model protein (catalase) were used. The visual aspect of the lyophilized cake, residual water content, and enzymatic activity recovery of catalase were assessed after each lyophilization cycle and after 1 month of storage of the lyophilized product at 4 degrees C and 25 degrees C. The freezing protocols allowing increasing nucleation temperature (precooled shelf and controlled nucleation by using ultrasounds or a nucleating agent) induced a faster sublimation step and higher sublimation rate homogeneity. Whatever the composition of the protective medium, applying the ultrasound technology made it possible to decrease the sublimation time by 14%, compared with the freezing method involving a constant shelf cooling rate of 1 degrees C/min. Concerning the enzyme activity recovery, the impact of the freezing protocol was observed only for the protective medium involving maltodextrin, a less effective protective agent than sucrose. Higher activity recovery results were obtained after storage when the ultrasound technology or the precooled shelf method was applied. Controlling ice nucleation during the freezing step of the lyophilization process improved the homogeneity of the sublimation rates, which will, in turn, reduce the intervial heterogeneity. The freeze-dryer prototype including

  11. Freeze-drying of nanosuspensions, part 3: investigation of factors compromising storage stability of highly concentrated drug nanosuspensions.

    PubMed

    Beirowski, Jakob; Inghelbrecht, Sabine; Arien, Albertina; Gieseler, Henning

    2012-01-01

    On the basis of a previously developed formulation and process guideline for lyophilized, highly concentrated drug nanosuspensions for parenteral use, it was the purpose of this study to demonstrate that the original nanoparticle size distribution can be preserved over a minimum period of 3 months, even if aggressive primary drying conditions are used. Critical factors were evaluated that were originally believed to affect storage stability of freeze-dried drug nanoparticles. It was found that the nature and concentration of the steric stabilizer, such as Poloxamer 338 and Cremophor EL, are the most important factors for long-term stability of such formulations, independent of the used drug compound. The rational choice of an adequate steric stabilizer, namely Poloxamer 338, in combination with various lyoprotectants seems crucial to prevent physical instabilities of the lyophilized drug nanoparticles during short-term stability experiments at ambient and accelerated conditions. A 200 mg/mL concentration of nanoparticles could successfully be stabilized over the investigated time interval. In the course of the present experiments, polyvinylpyrrolidone, type K15 was found superior to trehalose or sucrose in preserving the original particle size distribution, presumably based on its surface-active properties. Lastly, it was demonstrated that lower water contents are generally beneficial to stabilize such systems. Copyright © 2011 Wiley-Liss, Inc.

  12. Vis-NIR hyperspectral imaging in visualizing moisture distribution of mango slices during microwave-vacuum drying.

    PubMed

    Pu, Yuan-Yuan; Sun, Da-Wen

    2015-12-01

    Mango slices were dried by microwave-vacuum drying using a domestic microwave oven equipped with a vacuum desiccator inside. Two lab-scale hyperspectral imaging (HSI) systems were employed for moisture prediction. The Page and the Two-term thin-layer drying models were suitable to describe the current drying process with a fitting goodness of R(2)=0.978. Partial least square (PLS) was applied to correlate the mean spectrum of each slice and reference moisture content. With three waveband selection strategies, optimal wavebands corresponding to moisture prediction were identified. The best model RC-PLS-2 (Rp(2)=0.972 and RMSEP=4.611%) was implemented into the moisture visualization procedure. Moisture distribution map clearly showed that the moisture content in the central part of the mango slices was lower than that of other parts. The present study demonstrated that hyperspectral imaging was a useful tool for non-destructively and rapidly measuring and visualizing the moisture content during drying process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Oligosaccharide-based Surfactant/Citric Acid Buffer System Stabilizes Lactate Dehydrogenase during Freeze-drying and Storage without the Addition of Natural Sugar.

    PubMed

    Ogawa, Shigesaburo; Kawai, Ryuichiro; Koga, Maito; Asakura, Kouichi; Takahashi, Isao; Osanai, Shuichi

    2016-06-01

    Experiments were conducted to assess the maintenance effects of oligosaccharide-based surfactants on the enzymatic activity of a model protein, lactate dehydrogenase (LDH), during freeze-drying and room temperature storage using the citric acid buffer system. Oligosaccharide-based surfactants, which exhibit a high glass transition temperature (Tg), promoted the eminent retention of enzymatic activity during these protocols, whereas monosaccharide-based surfactants with a low Tg displayed poor performance at high concentration, albeit much better than that of Tween 80 at middle concentration. The increase in the alkyl chain length did not exert positive effects as observed for the maintenance effect during freeze-thawing, but an amphiphilic nature and a glass forming ability were crucial for the effective stabilization at a low excipient concentration during freeze-drying. Even a low oligosaccharide-based surfactant content (0.1 mg mL(-1)) could maintain LDH activity during freeze-drying, but a high surfactant content (1.0 mg mL(-1)) was required to prevent buffer precipitation and retain high LDH activity on storage. Regarding storage, glass formation restricted molecular mobility in the lyophilized matrix, and LDH activity was effectively retained. The present results describe a strategy based on the glass-forming ability of surfactant-type excipients that affords a natural sugar-free formulation or an alternative use for polysorbate-type surfactants.

  14. A novel freeze-dried storage and preparation method for the determination of mycophenolic acid in plasma by high-performance liquid chromatography.

    PubMed

    Wang, Lei; Qiang, Wei; Li, Ying; Cheng, Zeneng; Xie, Mengmeng

    2017-09-01

    Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy consuming; in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze-dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze-dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high-performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5-50 μg mL -1 , with both intra- and inter-day precision being <7% and biases <10%. The freeze-dried samples were stable at ambient temperature for at least 40 days. This method was also successfully applied to the pharmacokinetic study of MPA in healthy volunteers. Pharmacokinetic parameters, such as maximum plasma concentration, time point of maximum plasma concentration and elimination half-life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible and energy saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Drying effects on the antioxidant properties of tomatoes and ginger.

    PubMed

    Gümüşay, Özlem Aktürk; Borazan, Alev Akpınar; Ercal, Nuran; Demirkol, Omca

    2015-04-15

    In this study, the effects of four different drying processes, sun drying (SD), oven drying (OD), vacuum oven drying (VOD) and freeze drying (FD) for tomatoes (Solanum lycopersicum) and ginger (Zingiber officinale) in terms of thiolic and phenolic contents have been studied. Thiol content, total phenolic content (TPC), ascorbic acid (AA) content, and cupric ion reducing antioxidant capacity (CUPRAC) were determined in fresh and dried samples. Glutathione (GSH) and cysteine (Cys) were determined as the thiol contents of tomatoes and ginger. Significant losses were observed in the contents of TPC, AA, GSH and Cys and CUPRAC values in all samples that were dried using the thermal method. There was a statistically significant difference in the losses of the TPC, AA, and thiol contents between the use of thermal drying and freeze drying (except Cys in tomatoes) methods. Freeze dried tomato and ginger samples have been found to have better antioxidant properties. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Quality assessment of microwave-vacuum dried material with the use of computer image analysis and neural model

    NASA Astrophysics Data System (ADS)

    Koszela, K.; OtrzÄ sek, J.; Zaborowicz, M.; Boniecki, P.; Mueller, W.; Raba, B.; Lewicki, A.; Przybył, K.

    2014-04-01

    The farming area for vegetables in Poland is constantly changed and modified. Each year the cultivation structure of particular vegetables is different. However, it is the cultivation of carrots that plays a significant role among vegetables. According to the Main Statistical Office (GUS), in 2012 carrot held second position among the cultivated root vegetables, and it was estimated at 835 thousand tons. In the world we are perceived as the leading producer of carrot, due to the fourth place in the ranking of global producers. Poland is the largest producer of this vegetable in the EU [1]. It is also noteworthy, that the demand for dried vegetables is still increasing. This tendency affects the development of drying industry in our country, contributing to utilization of the product surplus. Dried vegetables are used increasingly often in various sectors of food products industry, due to high nutrition value, as well as to changing alimentary preferences of consumers [2-3]. Dried carrot plays a crucial role among dried vegetables, because of its wide scope of use and high nutrition value. It contains a lot of carotene and sugar present in the form of crystals. Carrot also undergoes many different drying processes, which makes it difficult to perform a reliable quality assessment and classification of this dried material. One of many qualitative properties of dried carrot, having important influence on a positive or negative result of the quality assessment, is color and shape. The aim of the research project was to develop a method for the analysis of microwave-vacuum dried carrot images, and its application for the classification of individual fractions in the sample studied for quality assessment. During the research digital photographs of dried carrot were taken, which constituted the basis for assessment performed by a dedicated computer programme developed as a part of the research. Consequently, using a neural model, the dried material was classified [4-6].

  17. Effects of hot air and freeze drying methods on antioxidant activity, colour and some nutritional characteristics of strawberry tree (Arbutus unedo L) fruit.

    PubMed

    Orak, H H; Aktas, T; Yagar, H; İsbilir, S Selen; Ekinci, N; Sahin, F Hasturk

    2012-08-01

    Antioxidant activity, colour and some nutritional properties of hot air and freeze-dried strawberry tree (Arbutus unedo L.) fruits were investigated. Additionally, the effects of two pre-treatments, namely ethyl oleate and water blanching, were compared in terms of drying characteristics. For determination of antioxidant activities in ethanol extracts, two different analytical methods were used: 1,1-diphenyl-2-picrylhydrazyl scavenging activity and β-carotene bleaching activity. As a result, the ethyl oleate pre-treatment shortened the drying time by hot air method and gave a higher 1,1-diphenyl-2-picrylhydrazyl scavenging activity (82.16 ± 0.34%), total phenolic content (7.62 ± 1.09 µg GAE/g extract), ascorbic acid content (236.93 ± 20.14 mg/100 g), besides hydromethylfurfural was not observed. Freeze-dried fruits exhibited higher ascorbic acid content (368.63 ± 17.16 mg/100 g) than those fresh fruits (231.33 ± 19.51 mg/100 g) and nearly 1,1-diphenyl-2-picrylhydrazyl activity (93.52 ± 0.41 %) to fresh fruits (94.03 ± 1.18%). Colour characteristics, sugar content and mineral contents of fruits were significantly affected by pre-treatments and drying methods (p < 0.05). It is concluded that the drying of strawberry tree fruits should bring a valuable and attractive foodstuff to food industry due to the rich nutritional components, antioxidant activity and colour. Another conclusion from this study is that the freeze-drying is the best drying method to keep the nutritional value, antioxidant activity and sensory properties of fruits.

  18. Impact of freeze-drying, mixing and horizontal transport on water vapor in the upper troposphere and lower stratosphere (UTLS)

    NASA Astrophysics Data System (ADS)

    Poshyvailo, Liubov; Ploeger, Felix; Müller, Rolf; Tao, Mengchu; Konopka, Paul; Abdoulaye Diallo, Mohamadou; Grooß, Jens-Uwe; Günther, Gebhard; Riese, Martin

    2017-04-01

    Water vapor in the upper troposphere and lower stratosphere (UTLS) is a key player in the global radiation budget. Therefore, a realistic representation of the water vapor distribution in this region and the involved control processes is critical for climate models, but largely uncertain hitherto. It is known that the extremely low temperatures around the tropical tropopause cause the dominant factor controlling water vapor in the lower stratosphere. Here, we focus on additional processes, such as horizontal transport between tropics and extratropics, small-scale mixing, and freeze-drying. We assess the sensitivities of simulated water vapor in the UTLS from simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS). CLaMS is a Lagrangian transport model, with a parameterization of small-scale mixing (model diffusion) which is coupled to deformations in the large-scale flow. First, to assess the robustness of water vapor with respect to the meteorological datasets we examine CLaMS driven by ECMWF ERA-Interim and the Japanese 55-year reanalysis. Second, to investigate the effects of small-scale mixing we vary the parameterized mixing strength in the CLaMS model between the reference case with the mixing strength optimized to reproduce atmospheric trace gas observations and a purely advective simulation with parameterized mixing turned off. Also calculation of Lagrangian cold points gives further insight of the processes involved. Third, to assess the effects of horizontal transport between the tropics and extratropics we carry out sensitivity simulations with horizontal transport barriers along latitude circles at the equator, 15°N/S and 35°N/S. Finally, the impact of Antarctic dehydration is estimated from additional sensitivity simulations with switched off freeze-drying in the model at high latitudes of 50°N/S. Our results show that the uncertainty in the tropical tropopause temperatures between current reanalysis datasets causes significant

  19. Effect of Sex on Flavor-related and Functional Compounds in Freeze-dried Broth Made from Korean Native Chicken

    PubMed Central

    Jayasena, Dinesh D.; Jung, Samooel; Alahakoon, Amali U.; Nam, Ki Chang

    2014-01-01

    Studies on the flavour characteristics of meat-based broth, quantification of flavour-related and functional compounds, and factors affecting the availability of such compounds are minimal. The present study was designed to determine the effects of sex on flavor-related and functional compounds in freeze-dried broth (FDB) made from Korean native chickens (KNC). Male and female KNC from a commercial strain (WoorimatdagTM) were reared under similar commercial conditions. FDB was separately prepared using male and female birds aged 100 d (six birds of each sex) and analyzed for nucleotide, free amino acid, betaine, carnitine, carnosine, anserine, and creatine contents, and fatty acid composition. The levels of betaine, carnitine and creatine in FDB were not significantly different between the two sexes (p>0.05) in KNC. Carnosine and anserine were not detected in FDB samples. However, FDB from female chickens had significantly higher inosine-5-monophosphate and arachidonic acid contents than did FDB from male chickens. FDB prepared with male KNC contained higher levels of inosine, linoleic acid, glycine, alanine, lysine, and serine (p<0.05). However, glutamic acid, oleic acid, and DHA were present in comparable amounts (p>0.05) in FDB made from male and female KNC. Our findings suggest that the sex of KNC has significant effect on the contents of flavor-related compounds, but not functional compounds. PMID:26761282

  20. Effect of freeze-dried leek powder (FDLP) and nitrite level on processing and quality characteristics of fermented sausages.

    PubMed

    Tsoukalas, D S; Katsanidis, E; Marantidou, S; Bloukas, J G

    2011-02-01

    Fermented sausages were produced with 0.84% and 1.68% freeze-dried leek powder (FDLP), providing 75 and 150 mg/kg NaNO(3), respectively, and three levels of added nitrite (0, 75, and 150 mg/kg NaNO(2). A control treatment was also produced with 150 mg/kg NaNO(2). Sausages with FDLP were darker and yellower (p<0.05) than the control. Higher FDLP levels produced less red, yellower and darker sausages (p<0.05). Lower FDLP levels resulted in higher (p<0.05) sensory scores for external appearance, flavour and overall acceptability. No differences were found among the treatments with FDLP plus 75 or 150 ppm NaNO(2) in TBA value, lightness, redness (cross section), redness stability, yellowness, texture parameters and sensory firmness, flavour and overall acceptability. The use of 0.84% FDLP and 75 ppm NaNO₂ is considered more appropriate for the production of fermented sausages, as it results in a 50% reduction in added nitrite. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Protective Effect of Boiled and Freeze-dried Mature Silkworm Larval Powder Against Diethylnitrosamine-induced Hepatotoxicity in Mice.

    PubMed

    Cho, Jae-Min; Kim, Kee-Young; Ji, Sang-Deok; Kim, Eun-Hee

    2016-09-01

    Hepatocellular carcinoma (HCC) is a representative inflammation-associated cancer and known to be the most frequent tumors. HCC may also induce important pro- and anti-tumor immune reactions. However, the underlying mechanisms are unsatisfactorily identified. We investigated the protective effect of boiled and freeze-dried mature silkworm larval powder (BMSP) on diethylnitrosamine (DEN)-induced hepatotoxicity in mice. Mice were fed with diet containing BMSP (0.1, 1, and 10 g/kg) for two weeks and DEN (100 mg/kg, intraperitoneally) was injected 18 hours before the end of this experiment. Liver toxicity was determined in serum and histopathological examination was assessed in the liver tissues. Infiltration of immune cells and expressions of inflammatory cytokines and chemokines were also examined. Pretreatment with BMSP reduced necrotic and histopathological changes induced by DEN in the liver. Measurement of serum biochemical indicators, the levels of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase, showed that pretreatment with BMSP also decreased DEN-induced hepatotoxicity. In addition, BMSP inhibited the macrophage and CD31 infiltration in a dose-dependent manner. The expressions of interleukin-1β, IFN-γ and chemokines for T cell activation were decreased in BMSP pretreatment groups. BMSP may have a protective effect against acute liver injury by inhibiting necrosis and inflammatory response in DEN-treated mice.

  2. Freeze-Dried Sulfur-Graphene Oxide-Carbon Nanotube Nanocomposite for High Sulfur-Loading Lithium/Sulfur Cells.

    PubMed

    Hwa, Yoon; Seo, Hyeon Kook; Yuk, Jong-Min; Cairns, Elton J

    2017-11-08

    The ambient-temperature rechargeable lithium/sulfur (Li/S) cell is a strong candidate for the beyond lithium ion cell since significant progress on developing advanced sulfur electrodes with high sulfur loading has been made. Here we report on a new sulfur electrode active material consisting of a cetyltrimethylammonium bromide-modified sulfur-graphene oxide-carbon nanotube (S-GO-CTA-CNT) nanocomposite prepared by freeze-drying. We show the real-time formation of nanocrystalline lithium sulfide (Li 2 S) at the interface between the S-GO-CTA-CNT nanocomposite and the liquid electrolyte by in situ TEM observation of the reaction. The combination of GO and CNT helps to maintain the structural integrity of the S-GO-CTA-CNT nanocomposite during lithiation/delithiation. A high S loading (11.1 mgS/cm 2 , 75% S) S-GO-CTA-CNT electrode was successfully prepared using a three-dimensional structured Al foam as a substrate and showed good S utilization (1128 mAh/g S corresponding to 12.5 mAh/cm 2 ), even with a very low electrolyte to sulfur weight ratio of 4. Moreover, it was demonstrated that the ionic liquid in the electrolyte improves the Coulombic efficiency and stabilizes the morphology of the Li metal anode.

  3. Socket preservation using freeze-dried bone allograft with and without plasma rich in growth factors in dogs

    PubMed Central

    Samandari, Mohammad Hasan; Haghighat, Abbas; Torabinia, Nakisa; Taghian, Mehdi; Sadri, Leyli; Naemy, Vahid

    2016-01-01

    Background: Plasma rich in growth factors (PRGF) and freeze-dried bone allograft (FDBA) are shown to promote bone healing. This study was aimed to histologically and histomorphometrically investigate the effect of combined use of PRGF and FDBA on bone formation, and compare it to FDBA alone and control group. Materials and Methods: The distal roots of the lower premolars were extracted bilaterally in four female dogs. Sockets were randomly divided into FDBA + PRGF, FDBA, and control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 4 weeks. Sockets were assessed histologically and histomorphometrically. Data were analyzed by Kruskal–Wallis test followed by Mann–Whitney U-tests utilizing the SPSS software version 20. P < 0.05 was considered statistically significant. Results: While the difference in density of fibrous tissue in three groups was not statistically significant (P = 0.343), the bone density in grafted groups was significantly higher than the control group (P = 0.021). The least decrease in all socket dimensions was observed in the FDBA group. However, these differences were only significant in coronal portion at week 4. Regarding socket dimensions and bone density, the difference between FDBA and FDBA+PRGF groups was not significant in middle and apical portions. Conclusion: The superiority of PRGF+FDBA overFDBA in socket preservation cannot be concluded from this experiment. PMID:27857769

  4. Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen.

    PubMed

    Abrego, Guadalupe; Alvarado, Helen L; Egea, Maria A; Gonzalez-Mira, Elizabeth; Calpena, Ana C; Garcia, Maria L

    2014-10-01

    Pranoprofen (PF)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were optimized and characterized as a means of exploring novel formulations to improve the biopharmaceutical profile of this drug. These systems were prepared using the solvent displacement technique, with polyvinyl alcohol (PVA) as a stabilizer. A factorial design was applied to study the influence of several factors (the pH of the aqueous phase and the stabilizer, polymer and drug concentrations) on the physicochemical properties of the NPs. After optimization, the study was performed at two different aqueous phase pH values (4.50 and 5.50), two concentrations of PF (1.00 and 1.50 mg/mL), three of PVA (5, 10, and 25 mg/mL), and two of PLGA (9.00 and 9.50 mg/mL). These conditions produced NPs of a size appropriate particle size for ocular administration (around 350 nm) and high entrapment efficiency (80%). To improve their stability, the optimized NPs were lyophilized. X-ray, FTIR, and differential scanning calorimetry analysis confirmed the drug was dispersed inside the particles. The release profiles of PF from the primary nanosuspensions and rehydrated freeze-dried NPs were similar and exhibited a sustained drug delivery pattern. The ocular tolerance was assessed by an HET-CAM test. No signs of ocular irritancy were detected (score 0). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. Healthy offspring from freeze-dried mouse spermatozoa held on the International Space Station for 9 months

    PubMed Central

    Wakayama, Sayaka; Kamada, Yuko; Yamanaka, Kaori; Kohda, Takashi; Suzuki, Hiromi; Shimazu, Toru; Tada, Motoki N.; Osada, Ikuko; Nagamatsu, Aiko; Kamimura, Satoshi; Nagatomo, Hiroaki; Mizutani, Eiji; Ishino, Fumitoshi; Yano, Sachiko

    2017-01-01

    If humans ever start to live permanently in space, assisted reproductive technology using preserved spermatozoa will be important for producing offspring; however, radiation on the International Space Station (ISS) is more than 100 times stronger than that on Earth, and irradiation causes DNA damage in cells and gametes. Here we examined the effect of space radiation on freeze-dried mouse spermatozoa held on the ISS for 9 mo at –95 °C, with launch and recovery at room temperature. DNA damage to the spermatozoa and male pronuclei was slightly increased, but the fertilization and birth rates were similar to those of controls. Next-generation sequencing showed only minor genomic differences between offspring derived from space-preserved spermatozoa and controls, and all offspring grew to adulthood and had normal fertility. Thus, we demonstrate that although space radiation can damage sperm DNA, it does not affect the production of viable offspring after at least 9 mo of storage on the ISS. PMID:28533361

  6. The Palatability of Lopinavir and Ritonavir Delivered by an Innovative Freeze-Dried Fast-Dissolving Tablet Formulation

    PubMed Central

    Brantly, Alexandra M.; Drobonick, Alexandra L.; King, Hannah T.; Mesta, Daniel C.; Richards, Caroline G.; Lal, Manjari; Lai, Manshun

    2018-01-01

    Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir (LPV/r). Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT−) and FDTs containing LPV/r (FDT+). Rats showed no change in consumption patterns for the placebo FDT− compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term (23 h) consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT− formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs. PMID:29593900

  7. The Palatability of Lopinavir and Ritonavir Delivered by an Innovative Freeze-Dried Fast-Dissolving Tablet Formulation.

    PubMed

    Pittman, David W; Brantly, Alexandra M; Drobonick, Alexandra L; King, Hannah T; Mesta, Daniel C; Richards, Caroline G; Lal, Manjari; Lai, Manshun

    2018-01-01

    Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir (LPV/r). Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT-) and FDTs containing LPV/r (FDT+). Rats showed no change in consumption patterns for the placebo FDT- compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term (23 h) consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT- formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.

  8. Effects of Freeze-dried Mulberry on Antioxidant Activities and Fermented Characteristics of Yogurt during Refrigerated Storage.

    PubMed

    Sung, Jung-Min; Kim, Young-Boong; Kum, Jun-Seok; Choi, Yun-Sang; Seo, Dong-Ho; Choi, Hyun-Wook; Park, Jong-Dae

    2015-01-01

    This study investigated the effect of added freeze-dried mulberry fruit juice (FDMJ) (1, 3 and 5%) on the antioxidant activity and fermented characteristic of yogurt during refrigerated storage. A decrease in pH of yogurt and increase in acidity was observed during fermentation. The yogurts with FDMJ exhibited faster rate of pH reduction than control. Initial lactic acid bacteria count of yogurt was 6.49-6.94 Log CFU/g and increased above 9 Log CFU/g in control and 1% in FDMJ yogurt for 24 h. The total polyphenol and anthocyanin content of FDMJ yogurt was higher than that of control due to the presence of phytochemical contents in mulberry. Moreover, antioxidant activity such as DPPH and reducing power was highest 5% FDMJ yogurt. During cold storage, pH decreased or remained constant in all yogurts with values ranging from 4.08 to 4.78 units. In sensory evaluation, the score of 1% FDMJ yogurt was ranked higher when compared with other yogurts. It is proposed that mulberry fruit juice powder can be used to improve sensory evaluation and enhance functionality of yogurt.

  9. Efficacy of decalcified freeze-dried bone allograft in the regeneration of small osseous defect: A comparative study

    PubMed Central

    Jaiswal, Yashmi; Kumar, Sanjeev; Mishra, Vijay; Bansal, Puneet; Anand, Kumar Rakshak; Singh, Sukumar

    2017-01-01

    Aim: To access the efficacy of decalcified freeze-dried bone allograft (DFDBA) in the regeneration of bone following small osseous defect in minor oral surgery. Objectives: To evaluate the ability of DFDBA to enhance the rate of wound healing and assess radiographic bone density, pain, and infection preoperatively and postoperatively. Materials and Methods: Twenty patients with cysts were assessed. Ten patients were filled with DFDBA (Group 1) and ten without bone graft (Group 2), respectively. Radiographic bone density was assessed on preoperative, intraoperative, and postoperative radiographs on 1st day, 3rd month, and at 6th month using Adobe Photoshop CS6 - Grayscale histogram. Results: Bone density in Group 1 was found to be significantly higher than in Group 2 on 3rd and 6th month postoperatively with a P = 0.024 and P = 0.016 which was statistically significant. The percentage increase in bone density between both the group was determined and yielded no difference over a period of time, but the difference in percentage increase was markedly higher in Group 1 compared to Group 2 at all the time intervals. Conclusion: Bone formed as depicted by bone density is significantly higher when DFDBA is used in small bony defects. PMID:29386818

  10. Effects of Freeze-dried Mulberry on Antioxidant Activities and Fermented Characteristics of Yogurt during Refrigerated Storage

    PubMed Central

    2015-01-01

    This study investigated the effect of added freeze-dried mulberry fruit juice (FDMJ) (1, 3 and 5%) on the antioxidant activity and fermented characteristic of yogurt during refrigerated storage. A decrease in pH of yogurt and increase in acidity was observed during fermentation. The yogurts with FDMJ exhibited faster rate of pH reduction than control. Initial lactic acid bacteria count of yogurt was 6.49-6.94 Log CFU/g and increased above 9 Log CFU/g in control and 1% in FDMJ yogurt for 24 h. The total polyphenol and anthocyanin content of FDMJ yogurt was higher than that of control due to the presence of phytochemical contents in mulberry. Moreover, antioxidant activity such as DPPH and reducing power was highest 5% FDMJ yogurt. During cold storage, pH decreased or remained constant in all yogurts with values ranging from 4.08 to 4.78 units. In sensory evaluation, the score of 1% FDMJ yogurt was ranked higher when compared with other yogurts. It is proposed that mulberry fruit juice powder can be used to improve sensory evaluation and enhance functionality of yogurt. PMID:26877641

  11. The intrinsically disordered protein LEA7 from Arabidopsis thaliana protects the isolated enzyme lactate dehydrogenase and enzymes in a soluble leaf proteome during freezing and drying.

    PubMed

    Popova, Antoaneta V; Rausch, Saskia; Hundertmark, Michaela; Gibon, Yves; Hincha, Dirk K

    2015-10-01

    The accumulation of Late Embryogenesis Abundant (LEA) proteins in plants is associated with tolerance against stresses such as freezing and desiccation. Two main functions have been attributed to LEA proteins: membrane stabilization and enzyme protection. We have hypothesized previously that LEA7 from Arabidopsis thaliana may stabilize membranes because it interacts with liposomes in the dry state. Here we show that LEA7, contrary to this expectation, did not stabilize liposomes during drying and rehydration. Instead, it partially preserved the activity of the enzyme lactate dehydrogenase (LDH) during drying and freezing. Fourier-transform infrared (FTIR) spectroscopy showed no evidence of aggregation of LDH in the dry or rehydrated state under conditions that lead to complete loss of activity. To approximate the complex influence of intracellular conditions on the protective effects of a LEA protein in a convenient in-vitro assay, we measured the activity of two Arabidopsis enzymes (glucose-6-P dehydrogenase and ADP-glucose pyrophosphorylase) in total soluble leaf protein extract (Arabidopsis soluble proteome, ASP) after drying and rehydration or freezing and thawing. LEA7 partially preserved the activity of both enzymes under these conditions, suggesting its role as an enzyme protectant in vivo. Further FTIR analyses indicated the partial reversibility of protein aggregation in the dry ASP during rehydration. Similarly, aggregation in the dry ASP was strongly reduced by LEA7. In addition, mixtures of LEA7 with sucrose or verbascose reduced aggregation more than the single additives, presumably through the effects of the protein on the H-bonding network of the sugar glasses. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Product mass transfer resistance directly determined during freeze-drying cycle runs using tunable diode laser absorption spectroscopy (TDLAS) and pore diffusion model.

    PubMed

    Kuu, Wei Y; O'Bryan, Kevin R; Hardwick, Lisa M; Paul, Timothy W

    2011-08-01

    The pore diffusion model is used to express the dry layer mass transfer resistance, [Formula: see text], as a function of the ratio r(e)/?, where r(e) is the effective pore radius and ? is the tortuosity factor of the dry layer. Using this model, the effective pore radius of the dry layer can be estimated from the sublimation rate and product temperature profiles measured during primary drying. Freeze-drying cycle runs were performed using the LyoStar II dryer (FTS Systems), with real-time sublimation rate profiles during freeze drying continuously measured by tunable diode laser absorption spectroscopy (TDLAS). The formulations chosen for demonstration of the proposed approach include 5% mannitol, 5% sucrose, 5% lactose, 3% mannitol plus 2% sucrose, and a parenteral nutrition formulation denoted VitaM12. The three different methods used for determination of the product resistance are: (1) Using both the sublimation rate and product temperature profiles, (2) using the sublimation rate profile alone, and (3) using the product temperate profile alone. Unlike the second and third methods, the computation procedure of first method does not need solution of the complex heat and mass transfer equations.

  13. Survival of experimentally induced Toxoplasma gondii tissue cysts in vacuum packed goat meat and dry fermented goat meat sausages.

    PubMed

    Neumayerová, Helena; Juránková, Jana; Saláková, Alena; Gallas, Leo; Kovařčík, Kamil; Koudela, Břetislav

    2014-05-01

    Ingestion of raw or undercooked meat is a potential source of human toxoplasmosis. The aim of this study was to determine the viability of Toxoplasma gondii cysts in vacuum packed (VP) goat meat and in dry fermented sausages (DFS), and evaluate certain physical and chemical parameters, like water activity (aw), pH value, content of salt, dry matter and fat. A portion of muscle tissue from experimentally infected animals was used for production of VP meat with or without addition of 2.5% curing salt, and stored at 4 °C or at -20 °C. Results of bioassay showed that, samples of vacuum packed Toxoplasma positive meat without salt addition were alive after six weeks at 4 °C. Incubation at -20 °C supported the viability after 3 h, but not after 4 h. After 7 days in 2.5% of curing salt, samples of T. gondii VP goat meat were still viable, but not after 14 days at 4 °C. All the DFS samples were not positive for infective cysts which mean that, they do not pose a risk of T. gondii transmission. These data suggest that vacuum packaging increases the survival of T. gondii cysts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Heat and mass transfer scale-up issues during freeze-drying, I: atypical radiation and the edge vial effect.

    PubMed

    Rambhatla, Shailaja; Pikal, Michael J

    2003-01-01

    The aim of this study is to determine whether radiation heat transfer is responsible for the position dependence of heat transfer known as the edge vial effect. Freeze drying was performed on a laboratory-scale freeze dryer using pure water with vials that were fully stoppered but had precision cut metal tubes inserted in them to ensure uniformity in resistance to vapor flow. Sublimation rates were determined gravimetrically. Vials were sputter-coated with gold and placed at selected positions on the shelf. Average sublimation rates were determined for vials located at the front, side, and center of an array of vials. Sublimation rates were also determined with and without the use of aluminum foil as a radiation shield. The effect of the guardrail material and its contribution to the edge vial effect by conduction heat transfer was studied by replacing the stainless steel band with a low-thermal conductivity material (styrofoam). The emissivities (epsilon) of relevant surfaces were measured using an infrared thermometer. Sublimation rate experiments were also conducted with vials suspended off the shelf to study the role of convection heat transfer. It was found that sublimation rates were significantly higher for vials located in the front compared to vials in the center. Additional radiation shields in the form of aluminum foil on the inside door resulted in a decrease in sublimation rates for the front vials and to a lesser extent, the center vials. There was a significant decrease in sublimation rate for gold-coated vials (epsilon approximately 0.4) placed at the front of an array when compared to that of clear vials (epsilon approximately 0.9). In the case of experiments with vials suspended off the shelf, the heat transfer coefficient was found to be independent of chamber pressure, indicating that pure convection plays no significant role in heat transfer. Higher sublimation rates were observed when the steel band was used instead of Styrofoam while the

  15. Report on UQ and PCMM Analysis of Vacuum Drying for UFD S&T Gaps

    SciT

    M. Fluss

    2015-08-31

    This report discusses two phenomena that could affect the safety, licensing, transportation, storage, and disposition of the spent fuel storage casks and their contents (radial hydriding during drying and water retention after drying) associated with the drying of canisters for dry spent fuel storage. The report discusses modeling frameworks and evaluations that are, or have been, developed as a means to better understand these phenomena. Where applicable, the report also discusses data needs and procedures for monitoring or evaluating the condition of storage containers during and after drying. A recommendation for the manufacturing of a fully passivated fuel rod, resistantmore » to oxidation and hydriding is outlined.« less

  16. Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females—Double isotope sequential single-blind studies in menstruating women

    PubMed Central

    Önning, Gunilla; Hulthén, Lena

    2017-01-01

    Background The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption. Objective The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843). Study design With a single blinded placebo controlled sequential design, iron absorption from a light breakfast meal administered with or without capsules containing 1010 cfu freeze-dried Lp299v was studied in healthy female volunteers of fertile age. The methodology used was a double isotope technique (59Fe and 55Fe). Two studies were performed using the same protocol. Results In study 1, the absorption of iron from a meal without Lp299v was found to be 17.4 ± 13.4%, and from an identical meal with Lp299v was found to be 22.4 ± 17.3% (mean ± SD). This difference was statistically significant (p = 0.040, n = 14). In study 2, the absorption of iron from a meal without Lp299v was found to be 20.9 ± 13.1%, and from an identical meal with Lp299v found to be 24.5 ± 12.0% (mean ± SD, n = 28), which again was statistically significant (p = 0.003). Conclusion Freeze-dried Lp299v enhances the absorption of iron when administered together with a meal with a high iron bioavailability. Trial registration ClinicalTrials.gov Identifier: NCT02131870 PMID:29236734

  17. Point-of-injury Use of Reconstituted Freeze Dried Plasma as a Resuscitative Fluid: A Special Report for Prehospital Trauma Care

    DTIC Science & Technology

    2013-01-01

    Point-of-injury use of reconstituted freeze dried plasma as a resuscitative fluid: A special report for prehospital trauma care Elon Glassberg, MD...in- jury as part of the multidisciplinary efforts to improve trauma victims’ outcome. BACKGROUND Trauma is the leading cause of death among adults be...diabetes.1 Managing the burden of injuries from decades of wars has underscored the importance of trauma research aimed at reducing morbidity and

  18. A modified haemagglutination inhibition test for rubella antibodies, using standardized, freeze-dried reagents. Report of a comparative multi-centre trial.

    PubMed Central

    van Weemen, B.; Kacaki, J.

    1976-01-01

    A modified haemagglutination inhibition test for rubella antibodies, using standardized freeze-dried reagents, was developed and compared with haemagglutination inhibition tests using fresh erythrocytes. This comparison was made in collaboration with six European laboratories. A total of 4205 serum samples were tested. The results show that: (1) Sensitivity and reliability of the modified test are good; (2) the modified test can be performed in polystyrene microtitration plates. PMID:789763

  19. Application of Optical Coherence Tomography Freeze-Drying Microscopy for Designing Lyophilization Process and Its Impact on Process Efficiency and Product Quality.

    PubMed

    Korang-Yeboah, Maxwell; Srinivasan, Charudharshini; Siddiqui, Akhtar; Awotwe-Otoo, David; Cruz, Celia N; Muhammad, Ashraf

    2018-01-01

    Optical coherence tomography freeze-drying microscopy (OCT-FDM) is a novel technique that allows the three-dimensional imaging of a drug product during the entire lyophilization process. OCT-FDM consists of a single-vial freeze dryer (SVFD) affixed with an optical coherence tomography (OCT) imaging system. Unlike the conventional techniques, such as modulated differential scanning calorimetry (mDSC) and light transmission freeze-drying microscopy, used for predicting the product collapse temperature (Tc), the OCT-FDM approach seeks to mimic the actual product and process conditions during the lyophilization process. However, there is limited understanding on the application of this emerging technique to the design of the lyophilization process. In this study, we investigated the suitability of OCT-FDM technique in designing a lyophilization process. Moreover, we compared the product quality attributes of the resulting lyophilized product manufactured using Tc, a critical process control parameter, as determined by OCT-FDM versus as estimated by mDSC. OCT-FDM analysis revealed the absence of collapse even for the low protein concentration (5 mg/ml) and low solid content formulation (1%w/v) studied. This was confirmed by lab scale lyophilization. In addition, lyophilization cycles designed using Tc values obtained from OCT-FDM were more efficient with higher sublimation rate and mass flux than the conventional cycles, since drying was conducted at higher shelf temperature. Finally, the quality attributes of the products lyophilized using Tc determined by OCT-FDM and mDSC were similar, and product shrinkage and cracks were observed in all the batches of freeze-dried products irrespective of the technique employed in predicting Tc.

  20. Postharvest Ultrasound-Assisted Freeze-Thaw Pretreatment Improves the Drying Efficiency, Physicochemical Properties, and Macamide Biosynthesis of Maca (Lepidium meyenii).

    PubMed

    Chen, Jin-Jin; Gong, Peng-Fei; Liu, Yi-Lan; Liu, Bo-Yan; Eggert, Dawn; Guo, Yuan-Heng; Zhao, Ming-Xia; Zhao, Qing-Sheng; Zhao, Bing

    2018-04-01

    A novel technique of ultrasound-assisted freeze-thaw pretreatment (UFP) was developed to improve the drying efficiency of maca and bioactive amide synthesis in maca. The optimal UFP conditions are ultrasonic processing 90 min at 30 °C with 6 freeze-thaw cycles. Samples with freeze-thaw pretreatment (FP), ultrasound pretreatment (UP), and UFP were prepared for further comparative study. A no pretreatment (NP) sample was included as a control. The results showed that UFP improved the drying efficiency of maca slices, showing the highest effective moisture diffusivity (1.75 × 10 -9 m 2 /s). This result was further supported by low-field nuclear magnetic resonance (LF-NMR) analysis and scanning electron microscopy (SEM). The rehydration capacity and protein content of maca slices were improved by UFP. More importantly, contents of bioactive macamides and their biosynthetic precursors were increased in 2.5- and 10-fold, respectively. In conclusion, UFP is an efficient technique to improve drying efficiency, physicochemical properties, and bioactive macamides of maca, which can be applied in the industrial manufacture of maca products. © 2018 Institute of Food Technologists®.

  1. Effect of molecular weight and ratio of poly ethylene glycols' derivatives in combination with trehalose on stability of freeze-dried IgG.

    PubMed

    Mohammad Zadeh, Amir Hossein; Rouholamini Najafabadi, Abdolhosein; Vatanara, Alireza; Faghihi, Homa; Gilani, Kambiz

    2017-12-01

    The influence of poly ethylene glycol (PEG) at different molecular weights (MWs) and ratios was studied on the stability of freeze-dried immune globulin G (IgG). PEGs (600-4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations. Size-exclusion chromatography, infra-red spectroscopy, differential scanning calorimeter, and gel electrophoresis were performed to characterize lyophilized samples. Pure IgG demonstrated the highest aggregation of 5.77 ± 0.10% after process and 12.66 ± 0.50% as well as 44.69 ± 0.50% upon 1 and 2 months of storage at 45 °C, respectively. 5% W/V of PEGs 4000 in combination with 40% W/W trehalose, significantly suppressed aggregation, 0.05 ± 0.01%, with minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG molecules and secondary conformation were properly preserved in all formulations comparing native IgG. It could be concluded that appropriate concentration and MW of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried antibody through inserting additional supportive mechanisms of actions.

  2. Determination of orthodontic tooth movement and tissue reaction following demineralized freeze-dried bone allograft grafting intervention

    PubMed Central

    Seifi, Massoud; Ghoraishian, Seyed Ahmad

    2012-01-01

    Background: Socket preservation after tooth extraction is one of the indications of bone grafting to enhance preorthodontic condition. The aim of this study is to determine the effects of socket preservation on the immediate tooth movement, alveolar ridge height preservation and orthodontic root resorption. Materials and Methods: In a split-mouth technique, twelve sites in three dogs were investigated as an experimental study. Crushed demineralized freeze-dried bone allograft (DFDBA) (CenoBone®) was used as the graft material. The defects were made by the extraction of 3rd premolar. On one side of each jaw, the defects were preserved by DFDBA and defects of the other side left opened as the control group. Simultaneously the teeth adjacent to the defects were pulled together by a NiTi coil spring. After eight weeks, the amount of (OTM), alveolar height, and root resorption were measured. Analysis of variance was used for purpose of comparison. Results: There was a slight increase in OTM at grafted sites as they were compared to the control sites (P<0.05). Also a significant bone resorption in control site and successful socket preservation in experimental site were observed. Reduction of root resorption at the augmented site was significant compared to the normal healing site (P<0.05). Conclusion: Using socket preservation, tooth movement can be immediately started without waiting for the healing of the recipient site. This can provide some advantages like enhanced rate of OTM, its approved effects on ridge preservation that reduces the chance of dehiscence and the reduction of root resorption. PMID:22623939

  3. Strategies for multivariate modeling of moisture content in freeze-dried mannitol-containing products by near-infrared spectroscopy.

    PubMed

    Yip, Wai Lam; Gausemel, Ingvil; Sande, Sverre Arne; Dyrstad, Knut

    2012-11-01

    Accurate determination of residual moisture content of a freeze-dried (FD) pharmaceutical product is critical for prediction of its quality. Near-infrared (NIR) spectroscopy is a fast and non-invasive method routinely used for quantification of moisture. However, several physicochemical properties of the FD product may interfere with absorption bands related to the water content. A commonly used stabilizer and bulking agent in FD known for variation in physicochemical properties, is mannitol. To minimize this physicochemical interference, different approaches for multivariate correlation between NIR spectra of a FD product containing mannitol and the corresponding moisture content measured by Karl Fischer (KF) titration have been investigated. A novel method, MIPCR (Main and Interactions of Individual Principal Components Regression), was found to have significantly increased predictive ability of moisture content compared to a traditional PLS approach. The philosophy behind the MIPCR is that the interference from a variety of particle and morphology attributes has interactive effects on the water related absorption bands. The transformation of original wavelength variables to orthogonal scores gives a new set of variables (scores) without covariance structure, and the possibility of inclusion of interaction terms in the further modeling. The residual moisture content of the FD product investigated is in the range from 0.7% to 2.6%. The mean errors of cross validated prediction of models developed in the investigated NIR regions were reduced from a range of 24.1-27.6% for traditional PLS method to 15.7-20.5% for the MIPCR method. Improved model quality by application of MIPCR, without the need for inclusion of a large number of calibration samples, might increase the use of NIR in early phase product development, where availability of calibration samples is often limited. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

    PubMed Central

    Mogharehabed, Ahmad; Birang, Reza; Torabinia, Nakisa; Nasiri, Saman; Behfarnia, Parichehr

    2014-01-01

    Background: The accelerating effect of plasma rich in growth factors (PRGFs) in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm). The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm²). The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm²). The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm²). Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant. PMID:25225559

  5. Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

    PubMed

    Schrier, J A; Fink, B F; Rodgers, J B; Vasconez, H C; DeLuca, P P

    2001-10-07

    The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

  6. Through-vial impedance spectroscopy of the mechanisms of annealing in the freeze-drying of maltodextrin: the impact of annealing hold time and temperature on the primary drying rate.

    PubMed

    Smith, Geoff; Arshad, Muhammad Sohail; Polygalov, Eugene; Ermolina, Irina

    2014-06-01

    The study aims to investigate the impact of annealing hold time and temperature on the primary drying rate/duration of a 10% (w/v) solution of maltodextrin with an emphasis on how the mechanisms of annealing might be understood from the in-vial measurements of the ice crystal growth and the glass transition. The electrical impedance of the solution within a modified glass vial was recorded between 10 and 10(6) Hz during freeze-drying cycles with varying annealing hold times (1-5 h) and temperatures. Primary drying times decreased by 7%, 27% and 34% (1.1, 4.3 and 5.5 h) with the inclusion of an annealing step at temperatures of -15°C, -10°C and -5°C, respectively. The glass transition was recorded at approximately -16°C during the re-heating and re-cooling steps, which is close to the glass transition (Tg ') reported for 10% (w/v) maltodextrin and therefore indicates that a maximum freeze concentration (∼86%, w/w, from the Gordon-Taylor equation) was achieved during first freezing, with no further ice being formed on annealing. This observation, coupled to the decrease in electrical resistance that was observed during the annealing hold time, suggests that the reduction in the drying time was because of improved connectivity of ice crystals because of Ostwald ripening rather than devitrification. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Interruption of a dry-type transformer in no-load by a vacuum circuit-breaker

    NASA Astrophysics Data System (ADS)

    Vandenheuvel, W. M. C.; Daalder, J. E.; Boone, M. J. M.; Wilmes, L. A. H.

    1983-08-01

    Overvoltages generated during interruption of a dry type delta-star connected transformer in no load by a vacuum breaker were studied. During interruption of inrush current 37% of the phase-to-ground overvoltages were 5 pu, and 6% 7 pu. Comparison of experimental and theoretical results using Boyle's model shows no discrepancy for inrush currents and clean overvoltages from the steady-state interruption. Overvoltages due to repetitive reignitions (not covered by Boyle's model) are higher than the calculated values during steady-state switching.

  8. Drying-induced physico-chemical changes in cranberry products.

    PubMed

    Michalska, Anna; Wojdyło, Aneta; Honke, Joanna; Ciska, Ewa; Andlauer, Wilfried

    2018-02-01

    Sugar-free cranberry juice (XAD) and juice with 15% of maltodextrin were dried by freeze-, vacuum and spray drying methods. Total phenolics (589-6435mg/kg dry matter) including 5 flavonols, 3 phenolic acids, 2 procyanidins and 5 anthocyanins were stronger affected by juice formulation than by drying methods. Spray drying of juice, regardless of its formulation, was competitive to freeze drying in terms of polyphenols' retention. Increase in temperature up to 100°C during vacuum drying of XAD extracts resulted in degradation of polyphenolics (down to 4%), except chlorogenic acid. Its content increased with rise in temperature and accelerated hydroxymethylfurfural formation. The stronger the impact of drying, the more chlorogenic acid is present in cranberry products. In all powders analysed, formation of furoylmethyl amino acids was noted. Antioxidant capacity of cranberry products was influenced by juice formulation and was linked to content of polyphenols. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Impact of critical process and formulation parameters affecting in-process stability of lactate dehydrogenase during the secondary drying stage of lyophilization: a mini freeze dryer study.

    PubMed

    Luthra, Sumit; Obert, Jean-Philippe; Kalonia, Devendra S; Pikal, Michael J

    2007-09-01

    The stresses during the secondary-drying stage of lyophilization were investigated using a controlled humidity mini-freeze-dryer [Luthra S, Obert J-P, Kalonia DS, Pikal MJ. 2007. Investigation of drying stresses on proteins during lyophilization: Differentiation between primary and secondary-drying stresses on lactate dehydrogenase using a humidity controlled mini freeze-dryer. J Pharm Sci 96: 61-70.]. Lactate dehydrogenase (LDH), was formulated in: (1) Tween 80, (2) citrate buffer, and (3) both Tween 80 and citrate buffer. Protein activity recovery was measured as a function of relative humidity (RH), product temperature, and drying duration. Studies were also conducted with different concentrations of sucrose, sorbitol, and poly (vinyl pyrrolidone) (PVP). LDH stability was affected to a small extent by RH and significantly by drying temperature and duration. Complete stabilization of LDH was observed when lyophilized with sucrose and PVP but only a partial stabilization was observed with sorbitol. The mini-freeze-dryer enabled studying the process parameters independently, unlike a conventional study where these effects are generally convoluted. The results suggest that the stability of the protein is a function of the dynamics of the system during lyophilization. The origin of the stabilization effect of sucrose, which could, in principle, be attributed both to direct interaction with the protein or vitrification of the protein was elucidated using lyoprotectants that can either hydrogen bond well with the protein (sorbitol) or form a good glass (PVP). It appears both effects are required for complete stabilization of the protein. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

  10. Critically safe vacuum pickup for use in wet or dry cleanup of radioactive materials

    DOEpatents

    Zeren, Joseph D.

    1994-01-01

    A vacuum pickup of critically safe quantity and geometric shape is used in cleanup of radioactive materials. Collected radioactive material is accumulated in four vertical, parallel, equally spaced canisters arranged in a cylinder configuration. Each canister contains a filter bag. An upper intake manifold includes four 90 degree spaced, downward facing nipples. Each nipple communicates with the top of a canister. The bottom of each canister communicates with an exhaust manifold comprising four radially extending tubes that meet at the bottom of a centrally located vertical cylinder. The top of the central cylinder terminates at a motor/fan power head. A removable HEPA filter is located intermediate the top of the central cylinder and the power head. Four horizontal bypass tubes connect the top of the central cylinder to the top of each of the canisters. Air enters the vacuum cleaner via a hose connected to the intake manifold. Air then travels down the canisters, where particulate material is accumulated in generally equal quantities in each filter bag. Four air paths of bag filtered air then pass radially inward to the bottom of the central cylinder. Air moves up the central cylinder, through the HEPA filter, through a vacuum fan compartment, and exits the vacuum cleaner. A float air flow valve is mounted at the top of the central cylinder. When liquid accumulates to a given level within the central cylinder, the four bypass tubes, and the four canisters, suction is terminated by operation of the float valve.

  11. Modified atmosphere packaging and vacuum packaging for long period chilled storage of dry-cured Iberian ham.

    PubMed

    Parra, V; Viguera, J; Sánchez, J; Peinado, J; Espárrago, F; Gutierrez, J I; Andrés, A I

    2010-04-01

    Dry-cured Iberian ham slices were stored under vacuum and under four different modified atmospheres (60/40=60%N(2)+40%CO(2); 70/30=70%N(2)+30%CO(2); 80/20=80%N(2)+20%CO(2); argon=70%argon+30%CO(2)) at 4+/-1 degrees C during 120 days. Gas composition, moisture content, pH, colour, pigment content, and lipid stability were measured, as well as sensory and microbial analysis were carried out throughout storage. A loss of intensity of red colour (a(*)-values) was observed during storage in ham slices (P<0.05). Consistently, MbFe(II)NO content also decreased throughout storage (P>0.05). Slices of ham packed in 40%CO(2) (60/40) and 30%CO(2) (70/30) showed lower a(*)-values than the rest of the batches after 60 days (P<0.05), though differences were not evident after 120 days (P>0.05). TBARs values showed an upward trend during the storage of packaged slices (P<0.05). Vacuum-packed slices showed the lowest TBARs values and those packed with 40%CO(2), the highest. Sensory attributes did not vary significantly (P>0.05) throughout storage under refrigeration and packed either in vacuum or in modified atmospheres. No safety problems were detected in relation to the microbial quality in any case. 2009 Elsevier Ltd. All rights reserved.

  12. Vacuum-sealed microcavity formed from suspended graphene by using a low-pressure dry-transfer technique

    NASA Astrophysics Data System (ADS)

    Takahashi, K.; Ishida, H.; Sawada, K.

    2018-01-01

    We report the development of a microcavity drum sealed by suspended graphene. The drum is fabricated by using a low-pressure dry-transfer technique, which involves vacuum de-aeration between a graphene sheet and a substrate and raising the temperature to above the glass transition of the supporting poly(methyl methacrylate) film, which serves to increase the real contact area. The result is a suspended graphene sheet with a maximum diameter of 48.6 μm. The Raman spectrum of the suspended graphene has a 2D/G ratio of 1.79 and a few D peaks, which suggests that the material is high-quality single-layer graphene. The dry-transfer technique yields a vacuum-sealed microcavity drum 1.1 μm deep up to 4.5 μm in diameter. The Raman shift indicates that the suspended graphene is subjected to a tensile strain of 0.05%, which is attributed to the pressure difference between the evacuated cavity and the exterior gas.

  13. Phase formation of V{sub 2}O{sub 5}.xNb{sub 2}O{sub 5} compounds via gels and freeze-dried precursors

    SciT

    Langbein, Hubert; Mayer-Uhma, Tobias

    2009-03-05

    An X-ray powder diffraction study of the phase formation in the system V{sub 2}O{sub 5}/Nb{sub 2}O{sub 5} is performed. Freeze-dried ammonium vanadate and ammonium oxalato niobate, alkoxide-derived xerogels and a mixture of active oxides are used as precursors to compare the resulting phase composition. Thermal decomposition of the freeze-dried precursor is monitored with DTA/TG and mass spectrometry. In the quasi-binary system V{sub 2}O{sub 5}-Nb{sub 2}O{sub 5} metastable VNbO{sub 5}, V{sub 4}Nb{sub 18}O{sub 55}, VNb{sub 9}O{sub 25} and solid solutions of V{sub 2}O{sub 5} in TT-Nb{sub 2}O{sub 5} as also thermodynamically stable VNb{sub 9}O{sub 25} exist. The thermal decomposition of freeze-driedmore » vanadate-oxalatoniobate solution allows the synthesis of all these phases in a relative simple manner. Structural relationships between an intermediate phase and the product, or, in the case of solid-state reactions, between one of the starting oxide and the product, favour the desired reaction. Therefore, the structure of a former phase influences or directs the structure of the product similar to a topotactic reaction.« less

  14. The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications.

    PubMed

    Pikal, M J; Cardon, S; Bhugra, Chandan; Jameel, F; Rambhatla, S; Mascarenhas, W J; Akay, H U

    2005-01-01

    Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, Tg, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. THEORETICAL MODEL: The model is based on a set of coupled differential equations resulting from constraints imposed by conservation of energy and mass, where numerical results are obtained using finite element analysis. Use of the model proceeds via a "modular software package" supported by Technalysis Inc. (Passage/ Freeze Drying). This package allows the user to define the problem by inputing shelf temperature, chamber pressure, container properties, product properties, and numerical analysis

  15. Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability.

    PubMed

    Ramos Yacasi, Gladys Rosario; Calpena Campmany, Ana Cristina; Egea Gras, María Antonia; Espina García, Marta; García López, María Luisa

    2017-04-01

    The stabilization of flurbiprofen loaded poly-ɛ-caprolactone nanoparticles (FB-PɛCL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development. Optimization of the FD to improve long-term stability of ocular administration's FB-PɛCL-NPs. FB-PɛCL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components. Optimized FB-PɛCL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10 °C for 1 h, freezing at -50 °C for 4 h, PD at +5 °C and 0.140 mbar for 24 h and a SD at +45 °C during 10 h. These conditions showed 188.4 ± 1.3 nm, 0.087 ± 0.014, 85.5 ± 1.4%, 0.61 ± 0.12%, -16.4 ± 0.1 mV and 325 ± 7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD. An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.

  16. Drying effects on the antioxidant properties of polysaccharides obtained from Agaricus blazei Murrill.

    PubMed

    Wu, Songhai; Li, Feng; Jia, Shaoyi; Ren, Haitao; Gong, Guili; Wang, Yanyan; Lv, Zesheng; Liu, Yong

    2014-03-15

    Three polysaccharides (ABMP-F, ABMP-V, ABMP-A) were obtained from Agaricus blazei Murrill via methods such as freeze drying, vacuum drying and air drying, respectively. Their chemical compositions were examined, and antioxidant activities were investigated on the basis of assay for hydroxyl radical, DPPH radical, ABTS free radical scavenging ability and assay for Fe(2+)-chelating ability. Results showed that the three ABMPs have different physicochemical and antioxidant properties. Compared with air drying and vacuum drying methods, freeze drying method resulted to ABMP with higher neutral sugar, polysaccharide yield, uronic acid content, and stronger antioxidant abilities of hydroxyl radical, DPPH radical, ABTS radical scavenging and Fe(2+)-chelating. As a result, Agaricus blazei Murrill polysaccharides are natural antioxidant and freeze drying method serves as a good choice for the preparation of such polysaccharides and should be used to produce antioxidants for food industry. Copyright © 2014. Published by Elsevier Ltd.

  17. Evaluation of HEPA vacuum cleaning and dry steam cleaning in reducing levels of polycyclic aromatic hydrocarbons and house dust mite allergens in carpets

    PubMed Central

    Yu, Chang Ho; Yiin, Lih-Ming; Fan, Zhi-Hua (Tina); Rhoads, George G.

    2014-01-01

    Dry steam cleaning, which has gained recent attention as an effective method to reduce house dust mite (HDM) allergen concentration and loading in carpets, was evaluated in this study for its efficacy in lowering levels of polycyclic aromatic hydrocarbons (PAHs) as well as HDM allergens. Fifty urban homes with wail-to-wall carpets, mostly low-income and with known lead contamination, were studied in 2003 and 2004. Two carpet-cleaning interventions were compared: Repeated HEPA (High Efficiency Particulate Air filtered) vacuuming alone and repeated HEPA vacuuming supplemented with dry steam cleaning. Vacuum samples were collected to measure carpet loading of dust and contaminants immediately before and after cleaning. Paired comparisons were conducted to evaluate the effectiveness of the cleaning protocols in reducing the levels of PAHs and HDM allergens in carpets. The results indicated that both cleaning methods substantially reduced the loading of PAHs and HDM allergens as well as dust in carpets (p < 0.0001). The reductions in loading of dust (64.4%), PAHs (69.1%), and HDM allergens (85.5%), by dry steam cleaning plus repetitive HEPA vacuuming were larger than the reductions by regular HEPA vacuumin