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

Danni Suhaidi; Yao-Da Dong; Paul Wynne; Karen P Hapgood; David A V Morton

doi:10.3390/pharmaceutics15051447

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

Pharmaceutics. 2023 May 9;15(5):1447. doi: 10.3390/pharmaceutics15051447.

Authors

Danni Suhaidi¹, Yao-Da Dong², Paul Wynne³, Karen P Hapgood⁴, David A V Morton¹

Affiliations

¹ School of Engineering, Deakin University, Waurn Ponds, VIC 3216, Australia.
² Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
³ Medicines Manufacturing Innovation Centre, Monash University, Clayton, VIC 3168, Australia.
⁴ School of Engineering, Swinburne University, Hawthorn, VIC 3122, Australia.

Abstract

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.

Keywords: L-leucine; amorphous solid dispersions; bulk powder characterization; flowability enhancement; particle engineering; spray drying; surface modification.

Grants and funding

The authors would like to acknowledge the Australian Government for their support through the Australian Government Research Training Program Scholarship.