Effect of processing and formulation factors on Catalase activity in tablets
The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely 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.
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Materials
Catalase from bovine liver, with 2000–5000 units/mg (CAT) (BOC Sciences, USA) was used as the model enzyme. Dextran (DEX) (Dextran 40, Pharmacosmos, Denmark), mannitol (MAN) (Parteck® M200, Merck, Germany), and trehalose (TRH) (Trehalose dihydrate, Merck, Germany) were used as potential stabilizers. The formulation was kept simple to minimize the potentially complex interactions of other materials with CAT.
Rúben Martins Fraga, Michela Beretta, João F. Pinto, Martin Spoerk, Ožbej Zupančič, Joana T. Pinto, Amrit Paudel,
Effect of processing and formulation factors on Catalase activity in tablets, International Journal of Pharmaceutics,
2024, 124626, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124626.
Read also our introduction article on Mannitol here:
