Water loss from silicone tubing and effect on protein concentration during drug product manufacturing.

Silicone tubing is used in various unit operations during drug product (DP) manufacturing. Hold of protein formulations in silicone tubing over time may have an impact on product quality, particularly protein concentration. This study evaluated the change in protein concentration of a test monoclonal antibody (mAb) formulation over various hold times in silicone tubing as a function of tubing internal diameter (ID) and wall thickness. It was hypothesized that the rate of water diffusion through the semi-permeable membrane is a function of the tubing ID and wall thickness. The weight and protein concentration of various formulation-filled tubings over time was measured. The weight of water lost varied linearly with the change in protein concentration. It was observed to be independent of mAb type, formulation composition, and initial protein concentration for a given tubing ID and wall thickness. The effect of formulation water activity on the water loss rate was investigated. A mechanistic diffusion-based model was developed that predicts the change in tubing weight and therefore protein concentration over various hold times for a given formulation and tubing. Overall, this study suggests that water loss from silicone tubing affects protein concentration and should be monitored during DP process development and manufacturing.

Examining Acid Formation During the Selective Dehydration of Fructose to 5-Hydroxymethylfurfural in Dimethyl Sulfoxide and Water.

Sustainable conversion of biomass, including fructose dehydration to 5-hydroxymethylfurfural (HMF), remains a challenge. Fructose can be selectively dehydrated to HMF in dimethyl sulfoxide (DMSO) without addition of an acid catalyst. The role of DMSO is examined starting with either fructose or HMF in DMSO/water. With increasing DMSO content, it is observed that fructose conversion, HMF selectivity, and post-reaction solution acidity increase. Although DMSO degradation to sulfuric acid is a potential source of acidity and reactivity, a barium chloride precipitation test demonstrates that sulfate ions are not detectable after reaction, suggesting that DMSO is stable during reaction at 120 °C and 150 °C with oxygen present. Instead, the majority of the acidic species produced are formic acid, levulinic acid, and humins. These acids have a minimal effect on fructose conversion in DMSO. These results suggest that DMSO promotes fructose conversion mainly through solvation effects and not as an origin of acid catalysis. For HMF stabilization, the optimal molar fraction of DMSO in water is 0.20-0.43. Overall, these results indicate that DMSO can promote fructose dehydration to HMF at 120 °C.