Spray freezing into liquid versus spray-freeze drying: Influence of atomization on protein aggregation and biological activity

AbstractSpray freeze-drying is a process to directly produce high quality powders with short drying time. The difference of microstructures has a great influence on the physical properties of powders. However, during the spray freeze-drying process, the freezing degree of droplets in the drying chamber will change the product structure and affect the powder quality. In this study, the surface structure and morphology of dry powders were observed using scanning electron microscopy. The formation mechanism of droplet morphology during spray freeze-drying was analyzed. The results show that the rapid freezing process can produce finer microstructures.

Download Full-text

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Pharmaceutics ◽

10.3390/pharmaceutics13050615 ◽

2021 ◽

Vol 13 (5) ◽

pp. 615

Author(s):

Jason C. K. Lo ◽

Harry W. Pan ◽

Jenny K. W. Lam

Keyword(s):

Protein Aggregation ◽

Flow Rate ◽

Freeze Drying ◽

Gas Flow ◽

Feed Solution ◽

Solute Concentration ◽

Gas Flow Rate ◽

Aerosol Performance ◽

Spray Freeze Drying ◽

Induced Aggregation

The prospect of inhaled biologics has garnered particular interest given the benefits of the pulmonary route of administration. Pertinent considerations in producing inhalable dry powders containing biological medicines relate to aerosol performance and protein stability. Spray-freeze-drying (SFD) has emerged as an established method to generate microparticles that can potentially be deposited in the lungs. Here, the SFD conditions and formulation composition were evaluated using bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as the protein stabilizer. A factorial design analysis was performed to investigate the effects of BSA content, solute concentration of feed solution, and atomization gas flow rate on dispersibility (as an emitted fraction), respirability (as fine particle fraction), particle size, and level of protein aggregation. The atomization gas flow rate was identified as a significant factor in influencing the aerosol performance of the powder formulations and protein aggregation. Nonetheless, high atomization gas flow rate induced aggregation, highlighting the need to further optimize the formulation. Of note, all the formulations exhibited excellent dispersibility, while no fragmentation of BSA occurred, indicating the feasibility of SFD and the promise of HPβCD as an excipient.

Download Full-text

Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽

10.1038/s41541-021-00349-w ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Changjiao Gan ◽

Wenbo Luo ◽

Yunzhou Yu ◽

Zhouguang Jiao ◽

Sha Li ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Clostridium Botulinum ◽

Freeze Drying ◽

Botulinum Neurotoxin ◽

Secretory Iga ◽

Immune Protection ◽

Dry Powder ◽

Botulinum Neurotoxin A ◽

Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

Download Full-text

A comparative study of encapsulation of carotenoid enriched-flaxseed oil and flaxseed oil by spray freeze-drying and spray drying techniques

LWT ◽

10.1016/j.lwt.2021.111153 ◽

2021 ◽

Vol 143 ◽

pp. 111153

Author(s):

Aysel Elik ◽

Derya Koçak Yanık ◽

Fahrettin Göğüş

Keyword(s):

Comparative Study ◽

Spray Drying ◽

Freeze Drying ◽

Flaxseed Oil ◽

Drying Techniques ◽

Spray Freeze Drying

Download Full-text

Post-Processing Techniques for the Improvement of Liposome Stability

Pharmaceutics ◽

10.3390/pharmaceutics13071023 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1023

Author(s):

Ji Young Yu ◽

Piyanan Chuesiang ◽

Gye Hwa Shin ◽

Hyun Jin Park

Keyword(s):

Freeze Drying ◽

Protective Agent ◽

Post Processing ◽

Additional Process ◽

Spray Freeze Drying ◽

The Stability ◽

Processing Techniques ◽

The Impact ◽

Self Aggregation ◽

Liposome Stability

Liposomes have been utilized as a drug delivery system to increase the bioavailability of drugs and to control the rate of drug release at the target site of action. However, the occurrence of self-aggregation, coalescence, flocculation and the precipitation of aqueous liposomes during formulation or storage can cause degradation of the vesicle structure, leading to the decomposition of liposomes. To increase the stability of liposomes, post-processing techniques have been applied as an additional process to liposomes after formulation to remove water and generate dry liposome particles with a higher stability and greater accessibility for drug administration in comparison with aqueous liposomes. This review covers the effect of these techniques including freeze drying, spray drying and spray freeze drying on the stability, physicochemical properties and drug encapsulation efficiency of dry liposomes. The parameters affecting the properties of liposomes during the drying process are also highlighted in this review. In addition, the impact of using a protective agent to overcome such limitations of each process is thoroughly discussed through various studies.

Download Full-text