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

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.

Highlights

•  ASD technology has influence on particle morphology.

•  Compression behavior dominated by particle morphology.

•  Vacuum drum dried intermediate direct compressible into tablets.

•  Vacuum drum dried material shows better tabletability as milled extrudate.

•  ASD technology: no impact on tablet disintegration/dissolution

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.

Download the full research paper as PDF here: Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

See the article

2.1 Materials

Ritonavir   (purity   >   99.8%)   was   obtained   from   AbbVie   Inc. (North   Chicago,   US). Copovidone (polyvinylpyrrolidone–vinyl acetate copolymer, Kollidon® VA 64) was purchased from  BASF SE  (Ludwigshafen,  Germany), fumed silicon  dioxide  (Aerosil® 200) from  Evonik Industries  (Essen,  Germany), sorbitan monolaurate  (Span®  20)  from  CRODA  (Nettetal, Germany), dicalcium   phosphate anhydrous (DI-CAFOS® A60)   from   Chemische   Fabrik Budenheim  (Budenheim,  Germany), and  sodium  stearyl  fumarate  (PRUV®)  from  JRS Pharma  (Rosenberg,  Germany). Acetone  (Emprove®  Essential, purity  96%)  and  methanol (Emprove® Essential, purity 99.5%) were obtained from Merck KGaA (Darmstadt, Germany).

Barbara V. Schönfeld, Ulrich Westedt, Karl G. Wagner,
Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying,
International Journal of Pharmaceutics: X, 2021, 100102,
ISSN 2590-1567,
https://doi.org/10.1016/j.ijpx.2021.100102.

Read more on Sodium Stearyl Fumarate as a pharmaceutical excipient here: