Molecular Insights on Successful Reconstitution of Freeze-Dried Nanofibrillated Cellulose Hydrogel

Abstract

The diversity and safety of nanofibrillated cellulose (NFC) hydrogels have gained a vast amount of interest at the pharmaceutical site in recent years. Moreover, this biomaterial has a high potential to be utilized as a protective matrix during the freeze-drying of heat-sensitive pharmaceuticals and biologics to increase their properties for long-term storing at room temperature and transportation. Since freeze-drying and subsequent reconstitution have not been optimized for this biomaterial, we must find a wider understanding of the process itself as well as the molecular level interactions between the NFC hydrogel and the most suitable lyoprotectants. Herein we optimized the reconstitution of the freeze-dried NFC hydrogel by considering critical quality attributes required to ensure the success of the process and gained insights of the obtained experimental data by simulating the effects of the used lyoprotectants on water and NFC. We discovered the correlation between the measured characteristics and molecular dynamics simulations and obtained successful freeze-drying and subsequent reconstitution of NFC hydrogel with the presence of 300 mM of sucrose. These findings demonstrated the possibility of using the simulations together with the experimental measurements to obtain a more comprehensive way to design a successful freeze-drying process, which could be utilized in future pharmaceutical applications.

Near-infrared analysis of nanofibrillated cellulose aerogel manufacturing

“…To answer the need for improved methods, PAT must be applied to the process. Regarding the freeze-drying of biomaterials, our recent results indicate that depending on excipient and biomaterial concentrations, we obtain end products with different residual water contents and porosity (Koivunotko et al, 2021). In that study, we explained how excipients prevent aggregation of NFC hydrogel during freeze-drying facilitating its subsequent reconstitution.…”

“…S11. Complementary results of 0.8% NFC + 300 mM SUC and control NFC samples are also presented in Koivunotko et al, 2021.…”

“…Two widely used excipients trehalose (TRE) and sucrose (SUC) (Sigma-Aldrich, Germany) (Fig. 1), were chosen for this study based on our previous results (Koivunotko et al, 2021). 1.5% (m/V) nanofibrillated cellulose (NFC) hydrogel (GrowDex®) was obtained from UPM-Kymmene, Finland.…”

“…Prior to freeze-drying, the glass transition temperature of the maximally freeze concentrated sample (Tg') of the studied formulations was determined with differential scanning calorimetry (DSC) (Discovery 2500, TA instruments, Germany) to ensure correct primary drying temperature and to prevent collapsing of the samples as reported in Koivunotko et al (2021).…”

“…The morphology and electron density of 1.5% NFC + 300 mM SUC, 0.8% NFC + 300 mM SUC, and 1.5% NFC aerogels were studied in more detail with ptychographic X-ray computed tomography (PXCT) utilizing the OMNY instrument (Holler et al, 2018) at the cSAXS beamline at the Swiss Light Source, Paul Scherrer Institut (PSI), Switzerland. The experimental setup is described in detail in Koivunotko et al (2021), and the measurement and reconstruction parameters for the 0.8% NFC + 300 mM SUC and 1.5% NCF aerogel samples were also reported in that work. The 1.5% NFC + 300 mM SUC aerogel was placed at 2.4 mm downstream the focus, where the beam was about 8 μm in size, and the sample was scanned following the positions of a Fermat spiral with an average step size of 2 μm.…”