Production of amorphous solid dispersions ASD to circumvent drugs’ poor water solubility problems – a comparison between mature hot melt extrusion HME , spray drying and milling and innovative printing 2D and 3D technologies

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Production of amorphous solid dispersions to circumvent drugs’ poor water solubility problems with mature hot-melt extrusion and innovative 3D printing technology

Publication . Macedo, Joana; Pinto, João F.; Vervaet, Chris

The number of drugs with solubility constraints under development has been increasing, impacting the oral bioavailability, and leading to major challenges in the development of oral dosage forms. To circumvent this problem various strategies can be used, with amorphous solid dispersions (ASDs) receiving special attention. Hot-melt extrusion (HME) has been considered for the preparation of ASDs, as a solvent-free technology. Furthermore, the current approach by the pharmaceutical industry for the production of medicines is unable to meet the needs of each patient. Due to its flexibility and small-scale production, three-dimensional (3D) printing has received a lot of attention for the production of medicines on demand. The aim of this work was to study the feasibility of HME and fused deposition modelling (FDM) 3D printing for the production of ASDs and further preparation of solid oral dosage forms. Firstly, a design of experiments approach was applied to evaluate the influence of different formulation variables on the processability by HME and FDM and on the properties of the products prepared. The stability, upon storage, of the ASDs formed with celecoxib was studied. Based on these results, and on the good performance of poly(vinyl) alcohol, a comprehensive study on its processability based on the drug content and storage conditions was performed. Secondly, the precision and accuracy of FDM for the production of tablets was analysed, together with the effect of the printer and the nozzle diameter, based on critical quality attributes of the tablets. Lastly, the feasibility of FDM to prepare tablets with different drug doses, adapted to the needs of the patients, was evaluated. The work conducted improved the understanding of the variables influencing the thermal processing by HME and FDM, surprisingly with the drug content having little effect, and printer equipment and nozzle diameter showing to influence the precision of the critical attributes of the tablets. Overall, this project proved the ability of the combination of HME and FDM techniques to produce uniform and precise tablets, individualized according to the patient’s needs, containing ASDs.

2023-04Tese de doutoramento

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Entidade financiadora

Fundação para a Ciência e a Tecnologia

Número da atribuição

SFRH/BD/125212/2016