Transformation of Ritonavir Nanocrystal Suspensions into a Redispersible Drug Product via Vacuum Drum Drying

The present study explored vacuum drum drying (VDD) as potential drying technique for the solidification of crystalline ritonavir nanosuspensions prepared by wet-ball milling. In detail, the impact of drying protectants (mannitol, lactose, trehalose) added to the ritonavir nanosuspension was assessed in dependence of the drum temperature with respect to processibility via VDD, resulting intermediate powder properties, remaining nanoparticulate redispersibility and crystallinity. A clear impact of the glass transition temperature (T_g) of the drying protectant on the redispersibility/crystallinity of the VDD intermediate was observed. Increased T_g of the drying protectant was associated with improved redispersibility/crystallinity at a defined drum temperature.

Consequently, the high T_g-substance trehalose and lactose showed a better performance than mannitol at higher drum temperatures. However, the processability and related powder properties were not in accordance with this observation. Mannitol containing formulations showed superior processibility to those containing trehalose/lactose. Moreover, the impact of the tableting and encapsulation process on the redispersibility of the VDD intermediate was studied for a selected formulation. Neither process demonstrated a negative impact on redispersibility. In conclusion, vacuum drum drying is a promising drying technique for the solidification of nanosuspensions to result in dried powder still containing ritonavir nanoparticles while demonstrating acceptable to good downstream processibility to tablets/capsules.

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Materials

Ritonavir (RTV, purity > 99.8%) was obtained from AbbVie Inc. (North Chicago, USA). Copovidone (polyvinylpyrrolidone–vinyl acetate copolymer, Kollidon® VA 64, COP) was purchased from BASF SE (Ludwigshafen, Germany), sodium dodecyl sulfate (SDS), mannitol (Parteck M 200 Emprove® Essential) and trehalose dihydrate (Emprove® Expert) from Merck KGaA (Darmstadt, Germany), and lactose (InhaLac®140) from MEGGLE Pharma (Wasserburg am Inn, Germany). Zirconium oxide beads were obtained from NETZSCH (Selb, Germany). Capsules (Quali-V HPMC capsules, size 0, color opaque grey) were purchased from Qualicaps (Madrid, Spain).

Schönfeld, B.V., Westedt, U., Keller, BL. et al. Transformation of Ritonavir Nanocrystal Suspensions into a Redispersible Drug Product via Vacuum Drum Drying. AAPS PharmSciTech 23, 137 (2022). https://doi.org/10.1208/s12249-022-02283-z