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Impact of Porous Excipients on the Manufacturability and Product Performance of Solid Self-Emulsifying Drug Delivery Systems

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Abstract

FDA-approved self-emulsifying medicines rely on liquid-based formulations, which can exhibit limited stability and short shelf-lives. Solid self-emulsifying drug delivery systems (SEDDS) can improve such issues, but there is still a great need for identifying suitable porous carriers to convert liquid SEDDS into solids without impairing their mechanical properties, functionality, and industrial feasibility. The impact of SEDDS adsorption on tableting is also poorly understood. Therefore, solid SEDDS were prepared by adsorbing liquid SEDDS onto ten commercially available porous excipients. Products were assessed with respect to mechanical behavior, tabletability, and product performance. Adsorbing SEDDS onto porous excipients led to satisfactory stability, with the exception of Zeopharm® 600 due to its high alkalinity, and Neusilin® US2/UFL2, which caused quercetin to crystallize out of the liquid concentrate. SEDDS adsorption reduced the elastic recovery of most excipients, making tableting achievable using Aeroperl® 300 and Aerosil® 200/300. The impact of SEDDS on elastic recovery provides additional understanding on solid SEDDS manufacture process. Acceptable tablets were made via direct compression but with slow disintegration. Addition of a superdisintegrant (crospovidone 5% w/w) ensured tablet manufacturing without impairment of product performance. Solid SEDDS displayed several technical advantages over their liquid counterparts, but attention must be given to the properties of the porous excipient chosen. Drug-excipient interactions play a significant role in drug degradation and crystallization in solid SEDDS. Improved mechanical behavior upon adsorption led to well-composed tablets that performed satisfactorily in vitro upon addition of a superdisintegrant. This study provides an insight on excipient-oriented rational development of solid SEDDS.

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Acknowledgments

This research was funded by the Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR). The authors express their appreciation to the industrial advisor Dr. Jonathan Booth (AstraZeneca) for his valuable input and knowledge, and Sterling Glass for his assistance proof-reading this article. The University of Connecticut and AbbVie jointly participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N. Eagleville Rd, Storrs, Connecticut, 06269-3092, USA

    André O’Reilly Beringhs, Bruna Cristina Minatovicz, Bodhisattwa Chaudhuri & Xiuling Lu

  2. Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois, 60064, USA

    Geoff G. Z. Zhang

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  1. André O’Reilly Beringhs
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  2. Bruna Cristina Minatovicz
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  3. Geoff G. Z. Zhang
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  5. Xiuling Lu
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Correspondence to Xiuling Lu.

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Conflict of Interest

André O'Reilly Beringhs and Bruna Cristina Minatovicz are graduate students at the University of Connecticut; Bodhisattwa Chaudhuri and Xiuling Lu and professors at the University of Connecticut. They all have no additional conflicts of interest to report. Geoff G. Z. Zhang is an employee of AbbVie and may own AbbVie stock.

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Beringhs, A.O., Minatovicz, B.C., Zhang, G.G.Z. et al. Impact of Porous Excipients on the Manufacturability and Product Performance of Solid Self-Emulsifying Drug Delivery Systems. AAPS PharmSciTech 19, 3298–3310 (2018). https://doi.org/10.1208/s12249-018-1178-x

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  • DOI: https://doi.org/10.1208/s12249-018-1178-x

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