Methodology for rapid development of a continuous loss-in-weight feeding process

The pharmaceutical industry has been shifting towards continuous manufacturing, specifically for tablet production. Compared to batch processing, continuous tableting exhibits higher process efficiency, better process control, reduced footprint, and consistent product quality. Understanding mass flow variability and feed factor profile of raw materials in the loss-in-weight feeding process is essential for controlling continuous processes. Current literature has highlighted correlations between material properties and feeding performance. However, research still lacks an assessment of how feeder set-up options impact this performance.

This paper aims to fill the existing gap between material properties and feeder output to expedite the process development stage. A selection of commercially available excipients, crystalline APIs, spray-dried excipients, and protein-based excipients (nineteen in total) were characterized in terms of physical properties and rheological behavior. Volumetric feeding trials were conducted in a loss-in-weight feeder to obtain the feeding performance (mass flow RSD and feed factor profile curve). Partial least squares regression demonstrated that feeder performance can be estimated from material density, flowability, cohesion, charge density, and porosity. Additionally, experiments were conducted to assess the impact of feeding set-up options on feeding dynamics, enabling the development of a workflow for set-up and operating range definition. Applying this workflow to five different materials demonstrated sufficient accuracy in defining the feeder set-up parameters when compared to the experimental data results. The developed data-driven approach minimizes both material and time requirements, making it more efficient than a trial-and-error approach, which is essential for accelerating development.

Materials

Nineteen raw materials commonly used to produce tablets were selected for this study. From these, eight commercially available excipients, two APIs, two protein-based excipients, and seven spray-dried excipients (produced in-house). The selected excipients fulfill different functions within the formulation and include agglomerated anhydrous lactose and lactitol monohydrate (Supertab 40LL, DFE, Goch, Germany), spray dried lactose ( Supertab 11SD, DFE, Goch, Germany), anhydrous lactose (Supertab 22AN, DFE, Goch, Germany), microcrystalline cellulose (Avicel PH-101, FMC, Philadelphia, PA, USA and Pharmacel 112, DFE, Goch, Germany), croscarmellose sodium (Ac-di-sol, DuPont, Wilmington, DE, USA), sodium stearyl fumarate (Pruv, JRS Pharma, Rosenberg, Germany) and magnesium stearate (Ligamed MF-2-V, Peter Greven, Bad Münstereifel, Germany). As model APIs, two grades of paracetamol were selected: micronized paracetamol (APAP M) and fine powder paracetamol (APAP FP) (kindly provided by Mallinckrodt, Dublin, Ireland). Additionally, two protein-based excipients (excipients A and B) and seven spray-dried excipients (excipients C, D, E, F, G, H, and I) (Hovione, Lisbon, Portugal) were also tested.

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Ana Martins, Cláudia Moura, João Henriques, João A. Lopes,
Methodology for rapid development of a continuous loss-in-weight feeding process,
International Journal of Pharmaceutics, 2025, 125434, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2025.125434.