Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Barbara V Schönfeld; Ulrich Westedt; Karl G Wagner

doi:10.1016/j.ijpx.2021.100102

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Int J Pharm X. 2021 Nov 3:3:100102. doi: 10.1016/j.ijpx.2021.100102. eCollection 2021 Dec.

Authors

Barbara V Schönfeld^{1

2}, Ulrich Westedt², Karl G Wagner¹

Affiliations

¹ Department of Pharmaceutical Technology, University of Bonn, Gerhard-Domagk-Straße 3, 53121 Bonn, Germany.
² AbbVie Deutschland GmbH & Co. KG, Knollstraße 50, 67061 Ludwigshafen, Germany.

Abstract

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Keywords: API, active pharmaceutical ingredient; ASD, amorphous solid dispersion; Amorphous solid dispersion; CP, compaction pressure; Compression analysis; D, tablet diameter; Downstream processing; FFC, flow function coefficient; HME, hot-melt extrusion; Hot-melt extrusion; LOD, loss on drying; P, breaking force; PSD, particle size distribution; PSmin, minimal punch separation; RTV, ritonavir; Ritonavir; SD, spray drying; SE, secondary electron; SEM, scanning electron microscope; SF, solid fraction; SSA, specific surface area; Spray drying; TER, Total elastic recovery; TS, tensile strength; Tg, glass transition temperature; V, volume; VDD, vacuum drum drying; Vacuum drum drying; X-ray μCT, X-ray microcomputed tomography; f1, difference factor; f2, similarity factor; n.d., not determined; na, not applicable; t, tablet thickness; w, tablet wall height.