Trehalose Crystallization During Freeze-Drying: Implications On Lyoprotection

Sundaramurthi, Prakash; Suryanarayanan, Raj

doi:10.1021/jz900338m

Cited by 74 publications

(73 citation statements)

References 20 publications

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“…The absence of diffraction peaks for α,α-trehalose 15 dehydrate was unexpected due to its high crystallizing nature and from the fact that its crystalline 16 form has been reported after freeze drying (Sundaramurthi and Suryanarayanan, 2010) …”

Section: Crystallinity 20mentioning

confidence: 99%

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Leclair

Cranston

Xing

et al. 2016

International Journal of Pharmaceutics

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4We have produced a thermally stable recombinant human type 5 adenoviral vector 5 (AdHu5) through spray drying with three excipient formulations (L-leucine, lactose/trehalose 6 and mannitol/dextran). Spray drying leads to immobilization of the viral vector which is believed 7 to prevent viral protein unfolding, aggregation and inactivation. The spray dried powders were 8 characterized by scanning electron microscopy, differential scanning calorimetry, Karl Fischer 9 titrations, and X-ray diffraction to identify the effects of temperature and atmospheric moisture 10 on the immobilizing matrix. Thermal stability of the viral vector was confirmed in vitro by 11 infection of A549 lung epithelial cells. Mannitol/dextran powders showed the greatest 12 improvement in thermal stability with almost no viral activity loss after storage at 20°C for 90 13 days (0.7 ± 0.3 log TCID 50 ) which is a significant improvement over the current -80 o C storage 14 protocol. Furthermore, viral activity was retained over short term exposure (72 hours) to 15 temperatures as high as 55°C. Conversely, all powders exhibited activity loss when subjected to 16 moisture due to amplified molecular motion of the matrix. Overall, a straightforward method 17 ideal for the production of thermally stable vaccines has been demonstrated through spray drying 18AdHu5 with a blend of mannitol and dextran and storing the powder under low humidity 19 conditions. 20 21

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Section: Crystallinity 20mentioning

confidence: 99%

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Leclair

Cranston

Xing

et al. 2016

International Journal of Pharmaceutics

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show abstract

“…Other routes are known that lead to amorphous solids; for example, mechanically damaging crystals (1) and removing water from hydrated crystals (2). Amorphous solids produced by cooling liquids are commonly called glasses.…”

Section: Introductionmentioning

confidence: 99%

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Sun

Zhu

et al. 2012

AAPS J

128

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Abstract. We review recent progress toward understanding and enhancing the stability of amorphous pharmaceutical solids against crystallization. As organic liquids are cooled to become glasses, fast modes of crystal growth can emerge. One such growth mode, the glass-to-crystal or GC mode, occurs in the bulk, and another exists at the free surface, both leading to crystal growth much faster than predicted by theories that assume diffusion defines the kinetic barrier of crystallization. These phenomena have received different explanations, and we propose that GC growth is a solid-state transformation enabled by local mobility in glasses and that fast surface crystal growth is facilitated by surface molecular mobility. In the second part, we review recent findings concerning the effect of polymer additives on crystallization in organic glasses. Low-concentration polymer additives can strongly inhibit crystal growth in the bulk of organic glasses, while having weaker effect on surface crystal growth. Ultra-thin polymer coatings can inhibit surface crystallization. Recent work has shown the importance of molecular weight for crystallization inhibitors of organic glasses, besides "direct intermolecular interactions" such as hydrogen bonding. Relative to polyvinylpyrrolidone, the VP dimer is far less effective in inhibiting crystal growth in amorphous nifedipine. Further work is suggested for better understanding of crystallization of amorphous organic solids and the prediction of their stability.

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“…Our observations are in agreement with the results obtained by other investigators in the development of paclitaxel-loaded liposomes [249,273]. In addition, Sundaramurthi and Suryanarayanan have demonstrated that trehalose has the tendency to undergo crystallization during lyophilization [275]. They suggested that partial crystallization occurs with annealing, and can be induced by other crystallizing solutes in the formulation such as buffer components.…”

Section: Effect Of Sucrose On Paclitaxel Retention and Psdsupporting

confidence: 92%

Development and Evaluation of Paclitaxel-Loaded Liposomal Formulations for Targeted Drug Delivery to Breast Cancer

Kannan¹

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Trehalose Crystallization During Freeze-Drying: Implications On Lyoprotection

Cited by 74 publications

References 20 publications

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Evaluation of excipients for enhanced thermal stabilization of a human type 5 adenoviral vector through spray drying

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Development and Evaluation of Paclitaxel-Loaded Liposomal Formulations for Targeted Drug Delivery to Breast Cancer

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