A Small-Scale, Material-Saving Approach to Rank-Order Lyophilized Formulations Based on Reconstitution Time

Purpose The goal of this manuscript is to describe a system amenable to automation that could estimate reconstitution times, and thus rank-order lyophilized systems using a small-scale, miniaturized, plate-based approach. Methods Multiple formulations of proprietary BMS protein molecules were lyophilized in 96-well plates with individual formulations assigned to each well. The lyophilized cakes were reconstituted using Water for Injection (WFI), and the 96-well plates were read using a UV–Vis plate reader. The corresponding reconstitution was monitored by observing the decreasing absorbance, or the increased transmittance within the wells over time. A minute amount of n -octanol was used to suppress foam that would otherwise interfere with the UV–Vis readings. Reconstitution times of the same formulations following lyophilization in a conventional vial system were also measured via visual inspection, for sake of comparison. Results There was linear correlation between data obtained from the miniaturized 96-well approach and that from the conventional manual reconstitution experiments. Qualitatively, the rank-ordering between the different formulations allowed rapid identification of best formulation compositions to facilitate reconstitution of the lyophilized cake. Conclusion This miniaturized high-throughput approach allows rapid screening and rank-ordering of different lyophilized formulations for optimal reconstitution time. The information obtained is invaluable in early development of parenteral products when material is scarce and data has to be gathered quickly. The novel approach presented here can be easily incorporated into larger automation workflows that have the potential to improve overall efficiency of the development process.