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Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding
23 Jul 2024 | Contributor(s):: Stauffer, F., Vanhoorne, V., Pilcer, G., Chavez, Pierre-François, Schubert, M. A., Vervaet, C., De Beer, T.
Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a...
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Variographic analysis: A new methodology for quality assurance of pharmaceutical blending processes
09 Jun 2023 | Contributor(s):: Sánchez-Paternina, Adriluz, Sierra-Vega, Nobel O., Cárdenas, Vanessa, Méndez, Rafael, Esbensen, Kim H., Romañach, Rodolfo J.
Analytical methods for real time monitoring of pharmaceutical blending processes are thoroughly validated but not the sampling methods. Variographic analysis was investigated as a method to determine the sampling and analytical errors when the drug concentration of pharmaceutical powder blends is...
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Theory of Sampling (TOS): A necessary and sufficient guarantee for reliable multivariate dara analysis in pharmaceutical manufacturing
09 Jun 2023 | Contributor(s):: Esbensen, Kim H, Romañach, Rodolfo, J.Ferrerira, Ana P., Menezes, Jose C., Tobyn, Mike, Román-Ospino, Andrés D.
Multivariate Analysis in the Pharmaceutical Industry provides industry practitioners with guidance on multivariate data methods and their applications over the lifecycle of a pharmaceutical product, from process development, to routine manufacturing, focusing on the challenges specific to each...
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The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products
09 Jun 2023 | Contributor(s):: Andres, G.P., Jones D.S., Senta-Loys Z., Almajaan A., Li S., Chevallier O., Elliot C., Healy A.M., Kelleher J.F., Madi A.M., Gilvary G.C., Tian Y.a
Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To...
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Raw material variability of an active pharmaceutical ingredient and its relevance for processability in secondary continuous pharmaceutical manufacturing
09 Jun 2023 | Contributor(s):: Stauffer, F, Vanhoorne, VPilcer, G, Chavez, PF, Rome, S, Schubert, MA, Aerts, L, De;Beer, T
Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product...
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Method transfer of a near-infrared spectroscopic method for blend uniformity in a poorly flowing and hygroscopic blend
09 Jun 2023 | Contributor(s):: Alvarado-Hernández, Bárbara, Scicolone, James, Ortega-Zuñiga, Carlos, Román-Ospino, Andrés, Colón-Lugo, Yleana, Aymat, Efrain, Sánchez, Eric, Muzzio, Fernando, Romañach, Rodolfo
The challenges in transferring and executing a near-infrared (NIR) spectroscopic method for croscarmellose (disintegrant) in binary blends for a continuous manufacturing (CM) process are presented. This work demonstrates the development of a NIR calibration model and its use to determine the...
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Managing API raw material variability during continuous twin-screw wet granulation
09 Jun 2023 | Contributor(s):: Stauffer, F, Vanhoorne, VPiker, G, Chavez, PF, Vervaet, C, De;Beer, T
Very few studies have investigated the impact of raw material variability upon the granule critical quality attributes (CQAs) produced via twin-screw wet granulation (i.e., granule size distribution, density, flowability). In this study, the impact of the raw material variability of an active...
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Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation
09 Jun 2023 | Contributor(s):: Willecke, N., Szepes, A., Wunderlich, M., Remon, J. P., Vervaet, C., De Beer, T.
The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin-screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation...
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Impact of blend properties and process variables on the blending performance
09 Jun 2023 | Contributor(s):: Bekaert, B, Grymonpre, W, Novikova, A, Vervaet, C, Vanhoorne, V
In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally,...
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Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders
09 Jun 2023 | Contributor(s):: Grymonpre, W., Verstraete, G., Vanhoorne, V., Remon, J. P., De Beer, T., Vervaet, C.
The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all...
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Determination of a quantitative relationship between material properties, process settings and screw feeding behavior via multivariate data-analysis
09 Jun 2023 | Contributor(s):: Bekaert, B, Penne, L, Grymonpre, W, Van Snick, B, Dhondt, J, Boeckx, J, Vogeleer, J, De Beer, T, Vervaet, C, Vanhoorne, V
In this study, a quantitative relationship between material properties, process settings and screw feeding responses of a high-throughput feeder was established via multivariate models (PLS). Thirteen divergent powders were selected and characterized for 44 material property descriptors. During...
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Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study
09 Jun 2023 | Contributor(s):: Roggo, Yves, Pauli, Victoria, Jelsch, Morgane, Pellegatti, Laurent, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Krumme, Markus
The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties...
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Continuous direct compression: Development of an empirical predictive model and challenges regarding PAT implementation
09 Jun 2023 | Contributor(s):: Bekaert, B., Van Snick, B., Pandelaere, K., Dhondt, J., Di Pretoro, G., De Beer, T., Vervaet, C., Vanhoorne, V.
In this study, an empirical predictive model was developed based on the quantitative relationships between blend properties, critical quality attributes (CQA) and critical process parameters (CPP) related to blending and tableting. The blend uniformity and API concentration in the tablets were...
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A PAT-based qualification of pharmaceutical excipients produced by batch or continuous processing
09 Jun 2023 | Contributor(s):: Hertrampf A., Müller H., Menezes J.C., Herdling T.
Pharmaceutical excipients have an influence on the main requirements for medicinal products (viz., quality, safety and efficacy) but also on their manufacturability. During product lifecycle it may become necessary to introduce minor changes (e.g., to continuously improve it) or major changes in...
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A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties
09 Jun 2023 | Contributor(s):: Bostijn, N, Dhondt, J, Ryckaert, A, Szabo, E, Dhondt, W, Van Snick, B, Vanhoorne, V, Vervaet, C, De Beer, T
In this study, the volumetric and gravimetric feeding behavior of 15 pharmaceutical powders on a low feed rate feeder was correlated with their material properties through a multivariate approach. The powders under investigation differ substantially in terms of material properties, making the...
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A multivariate raw material property database to facilitate drug product development and enable in-silico design of pharmaceutical dry powder processes
09 Jun 2023 | Contributor(s):: Van;Snick, B, Dhondt, JPandelaere, K, Bertels, J, Mertens, R, Klingeleers, D, Di, Pretoro, G, Remon, JP, Vervaet, C, De, Beer, T, Vanhoorne, V
In current study a holistic material characterization approach was proposed and an extensive raw material property database was developed including a wide variety of APIs and excipients with different functionalities. In total 55 different materials were characterized and described by over 100...