TY - JOUR
T1 - Effect of processing and formulation factors on Catalase activity in tablets
AU - Martins Fraga, Rúben
AU - Beretta, Michela
AU - Pinto, João F.
AU - Spörk, Martin
AU - Zupančič, Ožbej
AU - Fernandes Teixeira Pinto, Joana Filipa
AU - Paudel, Amrit
PY - 2024/8/28
Y1 - 2024/8/28
N2 - The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.
AB - The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.
KW - Aggregation
KW - Biologics
KW - Catalase
KW - Saccharides
KW - Spray-drying
KW - Tableting
KW - Tablets
UR - http://www.scopus.com/inward/record.url?scp=85202835515&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2024.124626
DO - 10.1016/j.ijpharm.2024.124626
M3 - Article
SN - 0378-5173
VL - 664
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 124626
ER -