Traditionally, the vial heat transfer coefficient (Kv) is measured using pure water due to the relatively constant temperature of ice during sublimation. However, anecdotal reports suggest Kv values measured using this method are not the same for the pharmaceutical product. The purpose of the present work is to explore the link between product resistance and edge vial effect by using constant resistance devices to mimic product resistance during Kv measurements.
A full shelf of 20 cc vials were filled with 10 mL water. The vials were stoppered with either low, medium, or high resistance stoppers to adjust the sublimation rate and product temperature (Tp)and loaded into a LyoStar 3. In each run, 30% of the water was allowed to sublimate. A total of 21 sublimation runs were carried out using different chamber pressures, shelf temperatures, and constant resistant stoppers. Vial heat transfer coefficients (Kv) were calculated for center and edge vials.
A nonlinear decrease in the edge vial effect (Kv,edge/Kv,center) was observed with an increasing batch vapor mass flow rate. The highest edge vial effect was associated with the lowest sublimation rate for high resistance device, while the lowest was observed for higher sublimation rate for low resistance device. The greater edge effect seen for higher resistance devices supports the anecdotal evidence that product Kv,edge values may be higher for product than for pure water. Additionally, a new approach to analyze Kv distributions was used which provides a holistic understanding of intra-batch heat transfer heterogeneity.
Dinesh Choudhary is a PhD candidate in Dr. Robin Bogner’s group at the University of Connecticut, where his research focuses on heat transfer in conventional freeze-drying and microwave-assisted freeze-drying of pharmaceuticals.
Speaker
Dinesh Choudhary
PhD Candidate, University of Connecticut
