Dynamical in-situ observation of the lyophilization and vacuum-drying processes of a model biopharmaceutical system by an environmental scanning electron microscope

0531984 - ÚPT 2021 RIV GB eng J - Journal Article
Vetráková, Ľubica - Neděla, Vilém - Runštuk, Jiří - Tihlaříková, Eva - Heger, D. - Shalaev, E.
Dynamical in-situ observation of the lyophilization and vacuum-drying processes of a model biopharmaceutical system by an environmental scanning electron microscope.
International Journal of Pharmaceutics. Roč. 585, JUL (2020), č. článku 119448. ISSN 0378-5173. E-ISSN 1873-3476
R&D Projects: GA ČR(CZ) GA19-08239S; GA ČR(CZ) GA19-03909S
Institutional support: RVO:68081731
Keywords : bovine serum albumin * freeze-drying * vacuum-drying * environmental scanning electron microscopy
OECD category: Pharmacology and pharmacy
Impact factor: 5.875, year: 2020
Method of publishing: Open access with time embargo
https://www.sciencedirect.com/science/article/abs/pii/S0378517320304324

The paper discusses the real-time monitoring of the changing sample morphology during the entire lyophilization (freeze-drying) and vacuum-drying processes of model biopharmaceutical solutions by using an environmental scanning electron microscope (ESEM), the device's micromanipulators were used to study the interior of the samples in-situ without exposing the samples to atmospheric water vapor. The individual collapse temperatures (T-c) of the formulations, pure bovine serum albumin (BSA) and BSA/sucrose mixtures, ranged from 5 to 29 degrees C. We evaluated the impact of the freezing method (spontaneous freezing, controlled ice nucleation, and spray freezing) on the morphologies of the lyophiles at the constant drying temperature of 20 degrees C. The formulations with T-c above 20 degrees C resulted in the lyophiles' morphologies significantly dependent on the freezing method. We interpret the observations as an interplay of the freezing rates and directionalities, both of which markedly influence the morphologies of the frozen formulations, and, subsequently, the drying process and the mechanical stability of the freeze-dried cake. The formulation with T-c below 20 degrees C yielded a collapsed cake with features independent of the freezing method. The vacuum-drying produced a material with a smooth and pore-free surface, where deep cracks developed at the end of the process.
Permanent Link: http://hdl.handle.net/11104/0310598