Feasibility and scale-up of co-precipitated Amorphous Solid Dispersions (ASDs) using High Shear Wet Milling (HSWM)

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Siddique, Mariam and McGowan, Mark and Smith, Kenneth and Janbon, Sophie and McCabe, Jim (2025) Feasibility and scale-up of co-precipitated Amorphous Solid Dispersions (ASDs) using High Shear Wet Milling (HSWM). In: Annual Conference of the British Association for Crystal Growth 2025, 2025-07-01 - 2025-07-03.

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Abstract

Amorphous solid dispersions (ASDs) are widely recognized as a key strategy for enhancing the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). By stabilizing the amorphous form of the API within a polymer matrix, ASDs offer improved dissolution profiles, enabling more effective oral drug delivery. Various manufacturing techniques have been developed to produce ASDs, including spray drying, hot melt extrusion, co-precipitation, and wet milling unique advantages and challenges in terms of scalability, process control, and material performance. High shear wet milling (HSWM) has emerged as a robust batch technique for co-precipitated ASD formation. It offers precise control over particle characteristics and has been successfully scaled up to 25L with Copovidone-based dispersions at CMAC, demonstrating strong potential for development and reproducibility. Recently, continuous manufacturing technologies such as the Taylor-Couette Flow Reactor have gained attention for their ability to maintain consistent process conditions, enable real-time optimization, and facilitate direct scalability (Laitinen et al., 2013). Despite its lower maximum shear rate compared to HSWM, the Taylor-Couette reactor has proven effective in forming ASDs with targeted API-polymer ratios, consistent bulk density, and minimal operational issues such as fouling or clogging. Optimization studies using black-box and multivariate design approaches have identified key parameters, including residence time, rotor speed, and temperature that influence process yield, product composition, and solvent removal efficiency. Long-duration proof-of-concept runs have further demonstrated process robustness in continuous ASD manufacturing, supporting the viability of platforms like Taylor-Couette reactor for future commercial-scale applications.

ORCID iDs

Siddique, Mariam ORCID logoORCID: https://orcid.org/0000-0002-3054-7192, McGowan, Mark, Smith, Kenneth, Janbon, Sophie and McCabe, Jim;
CORE (COnnecting REpositories)