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

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

Beringhs, André O'Reilly;Minatovicz, Bruna Cristina;Zhang, Geoff G Z;Chaudhuri, Bodhisattwa;Lu, Xiuling;
aaps pharmscitech 2018 Vol. 19 pp. 3298-3310
346
beringhs2018impactaaps

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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