A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

Autor: Véronique Hourquet, Bertrand Woinet, Didier Clénet, Hervé Ponceblanc, Manuel Vangelisti
Rok vydání: 2019
Předmět:
AIC
Akaike information criterion
Chemistry
Pharmaceutical
Dispersity
Pharmaceutical Science
02 engineering and technology
PSD
particle size distribution
030226 pharmacology & pharmacy
v/v
volume to volume ratio
Freeze-drying
DSC
differential scanning calorimetry
0302 clinical medicine
Drug Stability
Chlorocebus aethiops
Formulation screening
Tg
glass transition temperature
chemistry.chemical_classification
rHA
recombinant human albumin
DVS
dynamic vapor sorption
Yellow Fever Vaccine
NIRS
near infrared spectroscopy
General Medicine
Polymer
BIC
Bayesian information criterion
ASTM
American society for testing material
021001 nanoscience & nanotechnology
Dv
90
the maximum particle diameter below which 90% of the sample volume exists
0210 nano-technology
w/w
weight to weight ratio
Biotechnology
medicine.drug
Dv
50
the maximum particle diameter below which 50% of the sample volume exists
Materials science
Stability study
XRPD
X-ray powder diffraction
Yellow fever vaccine
Vaccines
Attenuated
Article
Excipients
03 medical and health sciences
95% CI
confidence interval at 95%
medicine
Animals
SEM
scanning electron microscopy
Live-attenuated vaccine stability
Vero Cells
ComputingMethodologies_COMPUTERGRAPHICS
CCID50
cell culture infectious dose 50
vYF
yellow fever virus produced in Vero cells
Chromatography
CMC
carboxymethyl cellulose
RH
relative humidity
Q10
quantity of particles in % volume having a size lower than 10 µm
RMC
relative moisture content
Freeze Drying
Breaking force
chemistry
Dv
10
the maximum particle diameter below which 10% of the sample volume exists
Micropellets
RSS
residual sum of squares
Zdroj: European Journal of Pharmaceutics and Biopharmaceutics
ISSN: 0939-6411
DOI: 10.1016/j.ejpb.2019.07.008
Popis: Graphical abstract
The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in order to optimize physico-chemical properties of the micropellets. Sugar/polymer-based formulations induced high glass transition temperature (Tg), adequate breaking force and attrition resistance of the SFD micropellets. These mechanical parameters and their stability are of considerable importance for the storage, the transport but also the filling process of the SFD micropellets. By adding excipients required to best preserve virus infectivity, an optimal sugar/polymer-based formulation was selected to build micropellets containing vYF. Monodisperse and dried micropellets with a diameter of about 530 µm were obtained, exhibiting similar potency to conventional freeze-dried product in terms of vYF infectious titer when both solid forms were kept under refrigerated conditions (2–8 °C). Comparable kinetics of degradation were observed for vYF formulated in micropellets or as conventional freeze-dried product during an accelerated stability study using incubations at 25 °C and 37 °C over several weeks. The results from this investigation demonstrate the ability to formulate live-attenuated viruses in micropellets. Pharmaceutical applications of this novel vaccine solid form are discussed.
Databáze: OpenAIRE
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