Bulk Flow Optimisation of Amorphous Solid Dispersion Excipient Powders through Surface Modification

Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their bulk flow and affects their utility and viability in terms of powder production, processing, and function. This study explores the effectiveness of L-leucine (L-leu) coprocessing in modifying the particle surface of ASD-forming materials. Various contrasting prototype coprocessed ASD excipients from both the food and pharmaceutical industries were examined for their effective coformulation with L-leu. The model/prototype materials included maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). The spray-drying conditions were set such that the particle size difference was minimised, so that it did not play a substantial role in influencing powder cohesion.

Scanning electron microscopy was used to evaluate the morphology of each formulation. A combination of previously reported morphological progression typical of L-leu surface modification and previously unreported physical characteristics was observed. The bulk characteristics of these powders were assessed using a powder rheometer to evaluate their flowability under confined and unconfined stresses, flow rate sensitivities, and compactability. The data showed a general improvement in maltodextrin, PVP K10, trehalose and gum arabic flowability measures as L-leu concentrations increased. In contrast, PVP K90 and HPMC formulations experienced unique challenges that provided insight into the mechanistic behaviour of L-leu. Therefore, this study recommends further investigations into the interplay between L-leu and the physico-chemical properties of coformulated excipients in future amorphous powder design. This also revealed the need to enhance bulk characterisation tools to unpack the multifactorial impact of L-leu surface modification.

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Maltodextrin DE18 and gum arabic were acquired from the Melbourne Food Depot (Melbourne, Australia). L-leu was purchased from Sigma-Aldrich (Castle Hill, Australia), and trehalose Powder was sourced from Swanson (Melbourne, Australia). Polyvinylpyrrolidone K10 (Average molecular weight 10,000 Da) and K90 (Average molecular weight 90,000 Da) were sourced from Sigma-Aldrich (Castle Hill, Australia). Hydroxypropyl methylcellulose E5LV (Methocel E5 Premium LV) was purchased from DuPont chemicals (Mississauga, ON, Canada), and hydroxypropyl methylcellulose K100M was purchased from Sigma-Aldrich (Castle Hill, Australia).

Suhaidi, D.; Dong, Y.-D.; Wynne, P.; Hapgood, K.P.; Morton, D.A.V. Bulk Flow Optimisation of Amorphous Solid Dispersion Excipient Powders through Surface Modification. Pharmaceutics 202315, 1447. https://doi.org/10.3390/pharmaceutics15051447

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