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Poly(butyl cyanoacrylate) (PBCA) is a biodegradable and biocompatible homopolymer which is used as a carrier matrix for drug delivery systems in the pharmaceutical industry. Typically, polymerization is carried out under aqueous conditions and results in molecular weights are mostly lower than 3000 g/mol due to the instability of the high molecular weight PBCA. However, the stability of polymer excipients is a major prerequisite for drug product development in the pharmaceutical industry. In this work, a reliable polymer synthesis strategy for PBCA was designed to control the molecular weight in a nonaqueous polymerization environment. The anionic polymerization process and the impact of key synthesis parameters were investigated. The results confirmed that the previously postulated depolymerization–repolymerization process (DPRP) in the literature can be used to tailor the molecular weight of PBCA. The amount of sodium methoxide present during the polymerization proved to be the key parameter to control the DPRP and the molecular weight as desired. In addition, it was discovered that end-capping the PBCA chain suppressed the DPRP and prevented monomer release by depriving the PBCA of its living character. Thus, neat PBCA polymer with varying molecular weights determined by Advanced Polymer Chromatography™ as well as end-capped PBCA were synthesized, and the improvement of the chemical and shelf-life stability were confirmed using NMR.

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 (Tg) of the drying protectant on the redispersibility/crystallinity of the VDD intermediate was observed. Increased Tg of the drying protectant was associated with improved redispersibility/crystallinity at a defined drum temperature. Consequently, the high Tg-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. Graphical Abstract