Process optimization of albumin-stabilized mitotane nanoparticle preparation by dual centrifugation and first lyophilization study
Permanent lenke
https://hdl.handle.net/10037/33518Dato
2022-05-13Type
MastergradsoppgaveMaster thesis
Forfatter
Zhang, Cindy Jia RuSammendrag
Albumin-stabilized mitotane nanoparticles intended for intravenous application can serve as a potential formulation for the treatment of adrenocortical carcinoma. However, the particle size of a nanoparticle-based formulation is crucial for the in vivo behavior of the nanoparticles following an intravenous injection. Prior to this project, the particle size of this nanoformulation had a mean of approximately 350 nm. Therefore, there is a need of a process optimization of albumin-stabilized mitotane nanoparticle preparation. The preparation of these nanoparticles was conducted by the method of dual centrifugation. In addition to this, lyophilization was carried out to get a first knowledge on how the particle size of the albumin-stabilized mitotane nanoparticles could be influenced by the process, as well as the influence of storing the freeze-dried product over a short period of time.
By varying different parameters such as the processing temperature and processing time for the DC, as well as using different sizes and amounts of ceramic beads as homogenization aid, and finally by using BSA solution adjusted to different pH, a reduced mean particle size was accomplished.
The results of the short-term stability study concluded the possibility of obtaining stable albumin-stabilized mitotane nanoparticles following the lyophilization process. Additionally, the nanoparticles in terms of particle size remained unchanged upon storage at refrigerated temperature. However, storage at room temperature need further investigation.
Keywords: mitotane; albumin; dual centrifugation; adrenocortical carcinoma; lyophilization; stability
Forlag
UiT Norges arktiske universitetUiT The Arctic University of Norway
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